Integration of energy metabolism (Homo sapiens)

From WikiPathways

Revision as of 23:28, 4 March 2011 by MaintBot (Talk | contribs)
Jump to: navigation, search
1-38, 76, 78, 85, 8655, 57, 62-6876, 78, 90-9522, 33, 70, 76, 78...6, 21-24, 28...20-24, 31-33161, 16369-7897-10012, 144167149, 158, 168152149, 164, 16533, 43-4722, 38, 4879-11, 137-14219-301676, 78, 90-9576, 78, 94, 9611, 101-11314, 147, 149-151, 154...6, 7, 22, 76, 78...17-24159-16322, 36-42133-13638, 50-5476, 78, 82, 86-89112, 114-1231355-6222, 70, 76, 78, 79133838, 49121-2415320-24, 117, 124...76, 78, 83, 84166143145-1517, 71, 76, 78, 81...21-2422, 36-38nucleoplasmmitochondrial matrixstored secretory granuleendoplasmic reticulum lumencytosolGastrin-releasing peptideHomeobox protein CDX-2IP3 receptor:IP3 complexcitrate lyase monomerLeptinAMPSynaptotagmin VATPVoltage-gated Calcium Channels Type Cav1 (closed)LKB-1Alpha-2A/2C Adrenergic ReceptorsAdrenaline/Noradrenaline:Alpha-2A/2C Adrenergic Receptor ComplexVoltage-gated Calcium Channels (pancreatic beta cell)O-acetylcholineSyntaxin-1A-Unc18-1 ComplexCalciumSUR1CalciumPKA catalytic subunitD-Xylulose 5-phosphateG-protein with G(s) alpha:GDP1-Phosphatidyl-D-myo-inositol 4,5-bisphosphateLigands of FFAR1 (GPR40)C PeptidePhospholipase C Beta: G(q) ComplexD-Fructose 6-phosphatealpha-D-glucoseCalciumG(q) alpha:GTP: G beta: G gamma Complex (pancreatic beta cell)G-protein alpha (s):GTP1,2-DiacylglycerolMuscarinic Acetylcholine Receptor M3GDPGs-activated adenylate cyclaseProglucagonGlucagonGTPH2OADPEpac2Fatty acidsAdenylate cyclase: G-protein alpha (s): GTP ComplexPP2A-ABdeltaC complexGlucagon-like Peptide-1 (Cleaved at N-terminus)ChREBP proteinPP2A-ABdeltaC complexG-beta:G-gamma dimerpChREBP (Thr 666)Signal Peptidase ComplexAdrenaline and NoradrenalineH2OSedoheptulose 7-phosphatePKA catalytic subunitUnc18-1ProglucagonpyrophosphatepChREBP (Ser 196, Thr 666)Voltage-gated Calcium Channels Type Cav1 (open)1D-myo-Inositol 1,4,5-trisphosphateADP/ATP translocase dimerPhosphorylated MARCKSAGPAT1ATPGTPD-Glyceraldehyde 3-phosphateFatty acid synthaseIP3 receptor homotetramerCa-channel (open)Insulin-Zinc-Calcium ComplexOrthophosphateAdenylyl cyclase (pancreatic beta cell)GTPAdenylate cyclase (Mg2+ cofactor)Insulin:Zinc:Calcium Complex in docked granuleC PeptidephosphoPFKFB1 dimermature GLP-1GDPProtein Kinase C, alpha type: Diacylglycerol ComplexADPProGIPGlucagon:GCGRPC1/3hTCF-4:Beta-cateninGustducin Complex (alpha, beta, gamma subunits)Adenylate Cyclase V or VIGPR119:Fatty Acid ComplexATPATPOrthophosphatePreproGIPG-protein i/o alpha:GTP:G-protein beta:G-protein gamma ComplexGLP-1: GLP-1R: Heterotrimeric G(s): GDP Complex3',5'-Cyclic AMPEpac2:cAMP ComplexGTPcAMP:PKA:AKAP79:IQGAP1 ComplexRap1-GTPGDPAMPK heterotrimer:AMPATPPreproglucagonGlucose-dependent Insulinotropic PolypeptidePotassium voltage-gated channels (beta cell, closed)SNAP-25Glucose-dependent Insulinotropic PolypeptidePKA:AKAP79:IQGAP1 ComplexTranscription factor GATA-4Inward Rectifying Potassium Channel (open)VAMP2/Synaptobrevin2ChREBP:MLXProGIPInsulin gene enhancer protein ISL-1Adenylate cyclase type V or VI: G-protein beta gamma ComplexG(q):GDP: G beta: G gamma Complex (pancreatic beta cell)ADPD-Erythrose 4-phosphatePotassium Channel, closed (pancreatic beta cell)transketolase dimerGDPG(q) alpha: GTP Complex (pancreatic beta cell)Glucagon receptor (GCGR)GTPADPGLP-1R: Heterotrimeric G(s): GDP ComplexGTPGLUT1 and GLUT2 (Pancreatic Beta Cell)G-protein i/o alpha:GDP:G-protein beta:G-protein gamma ComplexMARCKSG-protein alpha i/o:GTP ComplexGlucagon-like Peptide-1ADPEpac1:cAMP ComplexFree fatty acid receptor 1:fatty acid complexFree fatty acid receptor 1Heterotrimeric G-alpha(s): GTP:G-beta: G-gamma ComplexcAMP:PKA regulatory subunitDipeptidyl Peptidase 4AMPInward Rectifying Potassium Channel (closed)Pyruvate kinase, R isozymeG beta:G gamma ComplexMuscarinic Acetylcholine Receptor M3:Acetylcholine ComplexGDPADPGLP-1: GLP-1R: Heterotrimeric G(s): GTP ComplexGlucagon-like Peptide-1pChREBP(Ser 568)Protein kinase C, alpha typePFKFB1 dimerPhospholipase C Beta (pancreatic beta cell)Epac1Protein Kinase A, catalytic subunitsPAX6 isoform 1ACCtransaldolase 1Activated AMPK heterotrimerSNARE ComplexCa-channel (closed)Glucose-dependent Insulinotropic Polypeptide (Cleaved at N-terminus)Potassium Channel, open (pancreatic beta cell)Rap1-GDPATPADPATPalpha-D-glucoseGPR120: Fatty Acid ComplexD-ribose 5-phosphateAMPK heterotrimer (inactive)pChREBP (Thr 666)Core SNARE ComplexMLX proteinG-protein beta gamma Complex (candidates)ATPPotassium voltage-gated channels (beta cell, open)GDPPKA tetramerInactive PP2A-ABdeltaC complex656, 713612141589-114


Description

Many hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insulin mediates the storage of excess nutrients, glucagon is involved in the mobilization of energy resources in response to low blood glucose levels, principally by stimulating hepatic glucose output. Small doses of glucagon are sufficient to induce significant glucose elevations. These hormone-driven regulatory pathways enable the body to sense and respond to changed amounts of nutrients in the blood and demands for energy.
Glucagon and Insulin act through various metabolites and enzymes that target specific steps in metabolic pathways for sugar and fatty acids. The processes responsible for the long-term control of fat synthesis and short term control of glycolysis by key metabolic products and enzymes are annotated in this module as six specific pathways:
Pathway 1. Glucagon signalling in metabolic pathways: In response to low blood glucose, pancreatic alpha-cells release glucagon. The binding of glucagon to its receptor results in increased cAMP synthesis, and Protein Kinase A (PKA) activation.
Pathway 2. PKA mediated phosphorylation:PKA phosphorylates key enzymes, e.g., 6-Phosphofructo-2-kinase /Fructose-2,6-bisphosphatase (PF2K-Pase) at serine 36, and regulatory proteins, e.g., Carbohydrate Response Element Binding Protein (ChREBP) at serine 196 and threonine 666.
Insulin mediated responses to high blood glucose will be annotated in future versions of Reactome. In brief, the binding of insulin to its receptor leads to increased protein phosphatase activity and to hydrolysis of cAMP by cAMP phosphodiesterase. These events counteract the regulatory effects of glucagon.
Pathway 3: Insulin stimulates increased synthesis of Xylulose-5-phosphate (Xy-5-P). Activation of the insulin receptor results indirectly in increased Xy-5-P synthesis from Glyceraldehyde-3-phosphate and Fructose-6-phosphate. Xy-5-P, a metabolite of the pentose phosphate pathway, stimulates protein phosphatase PP2A.
Pathway 4: AMP Kinase (AMPK) mediated response to high AMP:ATP ratio: In response to diet with high fat content or low energy levels, the cytosolic AMP:ATP ratio is increased. AMP triggers a complicated cascade of events. In this module we have annotated only the phosphorylation of ChREBP by AMPK at serine 568, which inactivates this transcription factor.
Pathway 5: Dephosphorylation of key metabolic factors by PP2A: Xy-5-P activated PP2A efficiently dephosphorylates phosphorylated PF2K-Pase resulting in the higher output of F-2,6-P2 that enhances PFK activity in the glycolytic pathway. PP2A also dephosphorylates (and thus activates) cytosolic and nuclear ChREBP.
Pathway 6: Transcriptional activation of metabolic genes by ChREBP: Dephosphorylated ChREBP activates the transcription of genes involved in glucose metabolism such as pyruvate kinase, and lipogenic genes such as acetyl-CoA carboxylase, fatty acid synthetase, acyl CoA synthase and glycerol phosphate acyl transferase.
The illustration below summarizes this network of events. Black lines are metabolic reactions, red lines are negative regulatory events, and green lines are positive regulatory events (figure reused with permission from Veech (2003) - Copyright (2003) National Academy of Sciences, U.S.A.).

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Dillon JS, Tanizawa Y, Wheeler MB, Leng XH, Ligon BB, Rabin DU, Yoo-Warren H, Permutt MA, Boyd AE.; ''Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor.''; PubMed Europe PMC Scholia
  2. Hardie DG.; ''The AMP-activated protein kinase pathway--new players upstream and downstream.''; PubMed Europe PMC Scholia
  3. Pessin JE, Bell GI.; ''Mammalian facilitative glucose transporter family: structure and molecular regulation.''; PubMed Europe PMC Scholia
  4. Tao N, Wagner SJ, Lublin DM.; ''CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.''; PubMed Europe PMC Scholia
  5. Gromada J, Rorsman P.; ''Molecular mechanism underlying glucagon-like peptide 1 induced calcium mobilization from internal stores in insulin-secreting beta TC3 cells.''; PubMed Europe PMC Scholia
  6. Seino S, Chen L, Seino M, Blondel O, Takeda J, Johnson JH, Bell GI.; ''Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells.''; PubMed Europe PMC Scholia
  7. Rall T, Harris BA.; ''Identification of the lesion in the stimulatory GTP-binding protein of the uncoupled S49 lymphoma.''; PubMed Europe PMC Scholia
  8. Ansari IH, Longacre MJ, Stoker SW, Kendrick MA, O'Neill LM, Zitur LJ, Fernandez LA, Ntambi JM, MacDonald MJ.; ''Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells: Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion.''; PubMed Europe PMC Scholia
  9. Pinney SE, MacMullen C, Becker S, Lin YW, Hanna C, Thornton P, Ganguly A, Shyng SL, Stanley CA.; ''Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations.''; PubMed Europe PMC Scholia
  10. Morita H, Yano Y, Niswender KD, May JM, Whitesell RR, Wu L, Printz RL, Granner DK, Magnuson MA, Powers AC.; ''Coexpression of glucose transporters and glucokinase in Xenopus oocytes indicates that both glucose transport and phosphorylation determine glucose utilization.''; PubMed Europe PMC Scholia
  11. Bayewitch ML, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds WF, Vogel Z.; ''Inhibition of adenylyl cyclase isoforms V and VI by various Gbetagamma subunits.''; PubMed Europe PMC Scholia
  12. Fujise A, Mizuno K, Ueda Y, Osada S, Hirai S, Takayanagi A, Shimizu N, Owada MK, Nakajima H, Ohno S.; ''Specificity of the high affinity interaction of protein kinase C with a physiological substrate, myristoylated alanine-rich protein kinase C substrate.''; PubMed Europe PMC Scholia
  13. Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, Schultz G, Jakobs KH.; ''Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11.''; PubMed Europe PMC Scholia
  14. Macfarlane WM, O'Brien RE, Barnes PD, Shepherd RM, Cosgrove KE, Lindley KJ, Aynsley-Green A, James RF, Docherty K, Dunne MJ.; ''Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y.''; PubMed Europe PMC Scholia
  15. Gibson SK, Gilman AG.; ''Gialpha and Gbeta subunits both define selectivity of G protein activation by alpha2-adrenergic receptors.''; PubMed Europe PMC Scholia
  16. Leifert WR, Aloia AL, Bucco O, McMurchie EJ.; ''GPCR-induced dissociation of G-protein subunits in early stage signal transduction.''; PubMed Europe PMC Scholia
  17. Miki T, Nagashima K, Seino S.; ''The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells.''; PubMed Europe PMC Scholia
  18. Nauert JB, Rigas JD, Lester LB.; ''Identification of an IQGAP1/AKAP79 complex in beta-cells.''; PubMed Europe PMC Scholia
  19. Hollins B, Kuravi S, Digby GJ, Lambert NA.; ''The c-terminus of GRK3 indicates rapid dissociation of G protein heterotrimers.''; PubMed Europe PMC Scholia
  20. Delmeire D, Flamez D, Hinke SA, Cali JJ, Pipeleers D, Schuit F.; ''Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1.''; PubMed Europe PMC Scholia
  21. Yan L, Figueroa DJ, Austin CP, Liu Y, Bugianesi RM, Slaughter RS, Kaczorowski GJ, Kohler MG.; ''Expression of voltage-gated potassium channels in human and rhesus pancreatic islets.''; PubMed Europe PMC Scholia
  22. Tomita T, Masuzaki H, Noguchi M, Iwakura H, Fujikura J, Tanaka T, Ebihara K, Kawamura J, Komoto I, Kawaguchi Y, Fujimoto K, Doi R, Shimada Y, Hosoda K, Imamura M, Nakao K.; ''GPR40 gene expression in human pancreas and insulinoma.''; PubMed Europe PMC Scholia
  23. Hruz PW, Mueckler MM.; ''Structural analysis of the GLUT1 facilitative glucose transporter (review).''; PubMed Europe PMC Scholia
  24. Gullingsrud J, Kim C, Taylor SS, McCammon JA.; ''Dynamic binding of PKA regulatory subunit RI alpha.''; PubMed Europe PMC Scholia
  25. Girard CA, Shimomura K, Proks P, Absalom N, Castano L, Perez de Nanclares G, Ashcroft FM.; ''Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes.''; PubMed Europe PMC Scholia
  26. Smrcka AV, Hepler JR, Brown KO, Sternweis PC.; ''Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq.''; PubMed Europe PMC Scholia
  27. Bazarsuren A, Grauschopf U, Wozny M, Reusch D, Hoffmann E, Schaefer W, Panzner S, Rudolph R.; ''In vitro folding, functional characterization, and disulfide pattern of the extracellular domain of human GLP-1 receptor.''; PubMed Europe PMC Scholia
  28. Lacey RJ, Chan SL, Cable HC, James RF, Perrett CW, Scarpello JH, Morgan NG.; ''Expression of alpha 2- and beta-adrenoceptor subtypes in human islets of Langerhans.''; PubMed Europe PMC Scholia
  29. Akgoz M, Kalyanaraman V, Gautam N.; ''Receptor-mediated reversible translocation of the G protein betagamma complex from the plasma membrane to the Golgi complex.''; PubMed Europe PMC Scholia
  30. Henquin JC.; ''Triggering and amplifying pathways of regulation of insulin secretion by glucose.''; PubMed Europe PMC Scholia
  31. Gilon P, Henquin JC.; ''Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function.''; PubMed Europe PMC Scholia
  32. Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks P, Shimomura K, Haberland H, Carson DJ, Shield JP, Hattersley AT, Ashcroft FM.; ''Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.''; PubMed Europe PMC Scholia
  33. Underwood CR, Garibay P, Knudsen LB, Hastrup S, Peters GH, Rudolph R, Reedtz-Runge S.; ''Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.''; PubMed Europe PMC Scholia
  34. Grabsch H, Pereverzev A, Weiergräber M, Schramm M, Henry M, Vajna R, Beattie RE, Volsen SG, Klöckner U, Hescheler J, Schneider T.; ''Immunohistochemical detection of alpha1E voltage-gated Ca(2+) channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system.''; PubMed Europe PMC Scholia
  35. Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D.; ''Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding.''; PubMed Europe PMC Scholia
  36. Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, Ellis C, Elshourbagy NA, Goetz AS, Minnick DT, Murdock PR, Sauls HR, Shabon U, Spinage LD, Strum JC, Szekeres PG, Tan KB, Way JM, Ignar DM, Wilson S, Muir AI.; ''The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids.''; PubMed Europe PMC Scholia
  37. Lang J.; ''Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion.''; PubMed Europe PMC Scholia
  38. Wang JJ, Martin PR, Singleton CK.; ''Aspartate 155 of human transketolase is essential for thiamine diphosphate-magnesium binding, and cofactor binding is required for dimer formation.''; PubMed Europe PMC Scholia
  39. Ma L, Tsatsos NG, Towle HC.; ''Direct role of ChREBP.Mlx in regulating hepatic glucose-responsive genes.''; PubMed Europe PMC Scholia
  40. Jayakumar A, Tai MH, Huang WY, al-Feel W, Hsu M, Abu-Elheiga L, Chirala SS, Wakil SJ.; ''Human fatty acid synthase: properties and molecular cloning.''; PubMed Europe PMC Scholia
  41. Prentki M, Madiraju SR.; ''Glycerolipid metabolism and signaling in health and disease.''; PubMed Europe PMC Scholia
  42. Yang SN, Berggren PO.; ''Beta-cell CaV channel regulation in physiology and pathophysiology.''; PubMed Europe PMC Scholia
  43. Mueckler M, Kruse M, Strube M, Riggs AC, Chiu KC, Permutt MA.; ''A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity.''; PubMed Europe PMC Scholia
  44. Jacobson DA, Philipson LH.; ''Action potentials and insulin secretion: new insights into the role of Kv channels.''; PubMed Europe PMC Scholia
  45. Dallas-Yang Q, Shen X, Strowski M, Brady E, Saperstein R, Gibson RE, Szalkowski D, Qureshi SA, Candelore MR, Fenyk-Melody JE, Parmee ER, Zhang BB, Jiang G.; ''Hepatic glucagon receptor binding and glucose-lowering in vivo by peptidyl and non-peptidyl glucagon receptor antagonists.''; PubMed Europe PMC Scholia
  46. Martin BR, Farndale RW, Wong SK.; ''The role of Gs in activation of adenylate cyclase.''; PubMed Europe PMC Scholia
  47. Gerber SH, Südhof TC.; ''Molecular determinants of regulated exocytosis.''; PubMed Europe PMC Scholia
  48. Wojcikiewicz RJ, Luo SG.; ''Phosphorylation of inositol 1,4,5-trisphosphate receptors by cAMP-dependent protein kinase. Type I, II, and III receptors are differentially susceptible to phosphorylation and are phosphorylated in intact cells.''; PubMed Europe PMC Scholia
  49. Holz GG, Leech CA, Heller RS, Castonguay M, Habener JF.; ''cAMP-dependent mobilization of intracellular Ca2+ stores by activation of ryanodine receptors in pancreatic beta-cells. A Ca2+ signaling system stimulated by the insulinotropic hormone glucagon-like peptide-1-(7-37).''; PubMed Europe PMC Scholia
  50. Neuwald AF.; ''Galpha Gbetagamma dissociation may be due to retraction of a buried lysine and disruption of an aromatic cluster by a GTP-sensing Arg Trp pair.''; PubMed Europe PMC Scholia
  51. Naylor RN, Greeley SA, Bell GI, Philipson LH.; ''Genetics and pathophysiology of neonatal diabetes mellitus.''; PubMed Europe PMC Scholia
  52. Thomsen J, Kristiansen K, Brunfeldt K, Sundby F.; ''The amino acid sequence of human glucagon.''; PubMed Europe PMC Scholia
  53. Bratanova-Tochkova TK, Cheng H, Daniel S, Gunawardana S, Liu YJ, Mulvaney-Musa J, Schermerhorn T, Straub SG, Yajima H, Sharp GW.; ''Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion.''; PubMed Europe PMC Scholia
  54. Nagasumi K, Esaki R, Iwachidow K, Yasuhara Y, Ogi K, Tanaka H, Nakata M, Yano T, Shimakawa K, Taketomi S, Takeuchi K, Odaka H, Kaisho Y.; ''Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice.''; PubMed Europe PMC Scholia
  55. Sakiyama H, Wynn RM, Lee WR, Fukasawa M, Mizuguchi H, Gardner KH, Repa JJ, Uyeda K.; ''Regulation of nuclear import/export of carbohydrate response element-binding protein (ChREBP): interaction of an alpha-helix of ChREBP with the 14-3-3 proteins and regulation by phosphorylation.''; PubMed Europe PMC Scholia
  56. Pilkis SJ, el-Maghrabi MR, Claus TH.; ''Hormonal regulation of hepatic gluconeogenesis and glycolysis.''; PubMed Europe PMC Scholia
  57. Raybaud A, Baspinar EE, Dionne F, Dodier Y, Sauvé R, Parent L.; ''The role of distal S6 hydrophobic residues in the voltage-dependent gating of CaV2.3 channels.''; PubMed Europe PMC Scholia
  58. Dalman HM, Neubig RR.; ''Two peptides from the alpha 2A-adrenergic receptor alter receptor G protein coupling by distinct mechanisms.''; PubMed Europe PMC Scholia
  59. Gautam D, Han SJ, Duttaroy A, Mears D, Hamdan FF, Li JH, Cui Y, Jeon J, Wess J.; ''Role of the M3 muscarinic acetylcholine receptor in beta-cell function and glucose homeostasis.''; PubMed Europe PMC Scholia
  60. Leech CA, Castonguay MA, Habener JF.; ''Expression of adenylyl cyclase subtypes in pancreatic beta-cells.''; PubMed Europe PMC Scholia
  61. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T.; ''Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin.''; PubMed Europe PMC Scholia
  62. Winzell MS, Ahrén B.; ''G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes.''; PubMed Europe PMC Scholia
  63. Tanimura A, Nezu A, Morita T, Hashimoto N, Tojyo Y.; ''Interplay between calcium, diacylglycerol, and phosphorylation in the spatial and temporal regulation of PKCalpha-GFP.''; PubMed Europe PMC Scholia
  64. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y.; ''Inwardly rectifying potassium channels: their structure, function, and physiological roles.''; PubMed Europe PMC Scholia
  65. Rutter GA, Hill EV.; ''Insulin vesicle release: walk, kiss, pause ... then run.''; PubMed Europe PMC Scholia
  66. Holz GG, Kang G, Harbeck M, Roe MW, Chepurny OG.; ''Cell physiology of cAMP sensor Epac.''; PubMed Europe PMC Scholia
  67. Fujimoto K, Shibasaki T, Yokoi N, Kashima Y, Matsumoto M, Sasaki T, Tajima N, Iwanaga T, Seino S.; ''Piccolo, a Ca2+ sensor in pancreatic beta-cells. Involvement of cAMP-GEFII.Rim2. Piccolo complex in cAMP-dependent exocytosis.''; PubMed Europe PMC Scholia
  68. Lacey RJ, Cable HC, James RF, London NJ, Scarpello JH, Morgan NG.; ''Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans.''; PubMed Europe PMC Scholia
  69. Thorens B.; ''GLUT2 in pancreatic and extra-pancreatic gluco-detection (review).''; PubMed Europe PMC Scholia
  70. Babenko AP, Gonzalez G, Bryan J.; ''Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms.''; PubMed Europe PMC Scholia
  71. Peltonen JM, Pihlavisto M, Scheinin M.; ''Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha2-adrenoceptors.''; PubMed Europe PMC Scholia
  72. Thorell S, Gergely P, Banki K, Perl A, Schneider G.; ''The three-dimensional structure of human transaldolase.''; PubMed Europe PMC Scholia
  73. Richardson CC, Hussain K, Jones PM, Persaud S, Löbner K, Boehm A, Clark A, Christie MR.; ''Low levels of glucose transporters and K+ATP channels in human pancreatic beta cells early in development.''; PubMed Europe PMC Scholia
  74. Hirasawa A, Hara T, Katsuma S, Adachi T, Tsujimoto G.; ''Free fatty acid receptors and drug discovery.''; PubMed Europe PMC Scholia
  75. Shapiro H, Shachar S, Sekler I, Hershfinkel M, Walker MD.; ''Role of GPR40 in fatty acid action on the beta cell line INS-1E.''; PubMed Europe PMC Scholia
  76. Yajima H, Komatsu M, Sato Y, Yamada S, Yamauchi K, Sharp GW, Aizawa T, Hashizume K.; ''Norepinephrine inhibits glucose-stimulated, Ca2+-independent insulin release independently from its action on adenylyl cyclase.''; PubMed Europe PMC Scholia
  77. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, Ogi K, Hosoya M, Tanaka Y, Uejima H, Tanaka H, Maruyama M, Satoh R, Okubo S, Kizawa H, Komatsu H, Matsumura F, Noguchi Y, Shinohara T, Hinuma S, Fujisawa Y, Fujino M.; ''Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40.''; PubMed Europe PMC Scholia
  78. Smith NJ, Stoddart LA, Devine NM, Jenkins L, Milligan G.; ''The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1.''; PubMed Europe PMC Scholia
  79. Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB.; ''The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization.''; PubMed Europe PMC Scholia
  80. Gromada J, Rorsman P, Dissing S, Wulff BS.; ''Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release.''; PubMed Europe PMC Scholia
  81. Ostenson CG, Gaisano H, Sheu L, Tibell A, Bartfai T.; ''Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients.''; PubMed Europe PMC Scholia
  82. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR.; ''Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.''; PubMed Europe PMC Scholia
  83. Kurose H, Regan JW, Caron MG, Lefkowitz RJ.; ''Functional interactions of recombinant alpha 2 adrenergic receptor subtypes and G proteins in reconstituted phospholipid vesicles.''; PubMed Europe PMC Scholia
  84. Nobles M, Benians A, Tinker A.; ''Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells.''; PubMed Europe PMC Scholia
  85. Banno Y, Yada Y, Nozawa Y.; ''Purification and characterization of membrane-bound phospholipase C specific for phosphoinositides from human platelets.''; PubMed Europe PMC Scholia
  86. Schnell S, Schaefer M, Schöfl C.; ''Free fatty acids increase cytosolic free calcium and stimulate insulin secretion from beta-cells through activation of GPR40.''; PubMed Europe PMC Scholia
  87. Runge S, Schimmer S, Oschmann J, Schiødt CB, Knudsen SM, Jeppesen CB, Madsen K, Lau J, Thøgersen H, Rudolph R.; ''Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.''; PubMed Europe PMC Scholia
  88. Freitas Lima LC, Braga VA, do Socorro de França Silva M, Cruz JC, Sousa Santos SH, de Oliveira Monteiro MM, Balarini CM.; ''Adipokines, diabetes and atherosclerosis: an inflammatory association.''; PubMed Europe PMC Scholia
  89. Kang G, Leech CA, Chepurny OG, Coetzee WA, Holz GG.; ''Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells.''; PubMed Europe PMC Scholia
  90. Azpiazu I, Akgoz M, Kalyanaraman V, Gautam N.; ''G protein betagamma11 complex translocation is induced by Gi, Gq and Gs coupling receptors and is regulated by the alpha subunit type.''; PubMed Europe PMC Scholia
  91. Wu L, Fritz JD, Powers AC.; ''Different functional domains of GLUT2 glucose transporter are required for glucose affinity and substrate specificity.''; PubMed Europe PMC Scholia
  92. Kubota M, Wakamatsu K.; ''Peptide fragment of the m3 muscarinic acetylcholine receptor activates G(q) but not G(i2).''; PubMed Europe PMC Scholia
  93. Leech CA, Holz GG, Chepurny O, Habener JF.; ''Expression of cAMP-regulated guanine nucleotide exchange factors in pancreatic beta-cells.''; PubMed Europe PMC Scholia
  94. Noushmehr H, D'Amico E, Farilla L, Hui H, Wawrowsky KA, Mlynarski W, Doria A, Abumrad NA, Perfetti R.; ''Fatty acid translocase (FAT/CD36) is localized on insulin-containing granules in human pancreatic beta-cells and mediates fatty acid effects on insulin secretion.''; PubMed Europe PMC Scholia
  95. Lambert NA.; ''Dissociation of heterotrimeric g proteins in cells.''; PubMed Europe PMC Scholia
  96. Wiederkehr A, Wollheim CB.; ''Minireview: implication of mitochondria in insulin secretion and action.''; PubMed Europe PMC Scholia
  97. Del Guerra S, Bugliani M, D'Aleo V, Del Prato S, Boggi U, Mosca F, Filipponi F, Lupi R.; ''G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: the role of type 2 diabetes and fatty acids.''; PubMed Europe PMC Scholia
  98. Barg S, Eliasson L, Renström E, Rorsman P.; ''A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells.''; PubMed Europe PMC Scholia
  99. Havula E, Hietakangas V.; ''Glucose sensing by ChREBP/MondoA-Mlx transcription factors.''; PubMed Europe PMC Scholia
  100. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M.; ''Fatty acid signaling in the beta-cell and insulin secretion.''; PubMed Europe PMC Scholia
  101. Eason MG, Liggett SB.; ''Chimeric mutagenesis of putative G-protein coupling domains of the alpha2A-adrenergic receptor. Localization of two redundant and fully competent gi coupling domains.''; PubMed Europe PMC Scholia
  102. Tsuboi T, da Silva Xavier G, Holz GG, Jouaville LS, Thomas AP, Rutter GA.; ''Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells.''; PubMed Europe PMC Scholia
  103. Lin YW, MacMullen C, Ganguly A, Stanley CA, Shyng SL.; ''A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels.''; PubMed Europe PMC Scholia
  104. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T.; ''Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.''; PubMed Europe PMC Scholia
  105. Latour MG, Alquier T, Oseid E, Tremblay C, Jetton TL, Luo J, Lin DC, Poitout V.; ''GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo.''; PubMed Europe PMC Scholia
  106. Ma L, Robinson LN, Towle HC.; ''ChREBP*Mlx is the principal mediator of glucose-induced gene expression in the liver.''; PubMed Europe PMC Scholia
  107. Thorens B, Porret A, Bühler L, Deng SP, Morel P, Widmann C.; ''Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor.''; PubMed Europe PMC Scholia
  108. Colville CA, Seatter MJ, Jess TJ, Gould GW, Thomas HM.; ''Kinetic analysis of the liver-type (GLUT2) and brain-type (GLUT3) glucose transporters in Xenopus oocytes: substrate specificities and effects of transport inhibitors.''; PubMed Europe PMC Scholia
  109. Banki K, Halladay D, Perl A.; ''Cloning and expression of the human gene for transaldolase. A novel highly repetitive element constitutes an integral part of the coding sequence.''; PubMed Europe PMC Scholia
  110. Kang G, Joseph JW, Chepurny OG, Monaco M, Wheeler MB, Bos JL, Schwede F, Genieser HG, Holz GG.; ''Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells.''; PubMed Europe PMC Scholia
  111. Verghese GM, Johnson JD, Vasulka C, Haupt DM, Stumpo DJ, Blackshear PJ.; ''Protein kinase C-mediated phosphorylation and calmodulin binding of recombinant myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein.''; PubMed Europe PMC Scholia
  112. Sher E, Giovannini F, Codignola A, Passafaro M, Giorgi-Rossi P, Volsen S, Craig P, Davalli A, Carrera P.; ''Voltage-operated calcium channel heterogeneity in pancreatic beta cells: physiopathological implications.''; PubMed Europe PMC Scholia
  113. Lang J, Nishimoto I, Okamoto T, Regazzi R, Kiraly C, Weller U, Wollheim CB.; ''Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits.''; PubMed Europe PMC Scholia
  114. Dessauer CW, Chen-Goodspeed M, Chen J.; ''Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.''; PubMed Europe PMC Scholia
  115. Bavec A, Licar A.; ''Functional characterization of N-terminally GFP-tagged GLP-1 receptor.''; PubMed Europe PMC Scholia
  116. Sharp GW.; ''Mechanisms of inhibition of insulin release.''; PubMed Europe PMC Scholia
  117. McIntire WE.; ''Structural determinants involved in the formation and activation of G protein betagamma dimers.''; PubMed Europe PMC Scholia
  118. Gao Z, Young RA, Trucco MM, Greene SR, Hewlett EL, Matschinsky FM, Wolf BA.; ''Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis.''; PubMed Europe PMC Scholia
  119. Proks P, Arnold AL, Bruining J, Girard C, Flanagan SE, Larkin B, Colclough K, Hattersley AT, Ashcroft FM, Ellard S.; ''A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.''; PubMed Europe PMC Scholia
  120. Luvisetto S, Fellin T, Spagnolo M, Hivert B, Brust PF, Harpold MM, Stauderman KA, Williams ME, Pietrobon D.; ''Modal gating of human CaV2.1 (P/Q-type) calcium channels: I. The slow and the fast gating modes and their modulation by beta subunits.''; PubMed Europe PMC Scholia
  121. MacDonald PE, Wang G, Tsuk S, Dodo C, Kang Y, Tang L, Wheeler MB, Cattral MS, Lakey JR, Salapatek AM, Lotan I, Gaisano HY.; ''Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus.''; PubMed Europe PMC Scholia
  122. Vignali S, Leiss V, Karl R, Hofmann F, Welling A.; ''Characterization of voltage-dependent sodium and calcium channels in mouse pancreatic A- and B-cells.''; PubMed Europe PMC Scholia
  123. Peterhoff M, Sieg A, Brede M, Chao CM, Hein L, Ullrich S.; ''Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice.''; PubMed Europe PMC Scholia
  124. Digby GJ, Lober RM, Sethi PR, Lambert NA.; ''Some G protein heterotrimers physically dissociate in living cells.''; PubMed Europe PMC Scholia
  125. Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P.; ''Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.''; PubMed Europe PMC Scholia
  126. Ferrer J, Benito C, Gomis R.; ''Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans with and without NIDDM.''; PubMed Europe PMC Scholia
  127. Seino S, Iwanaga T, Nagashima K, Miki T.; ''Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice.''; PubMed Europe PMC Scholia
  128. Remaury A, Larrouy D, Daviaud D, Rouot B, Paris H.; ''Coupling of the alpha 2-adrenergic receptor to the inhibitory G-protein Gi and adenylate cyclase in HT29 cells.''; PubMed Europe PMC Scholia
  129. Veech RL.; ''A humble hexose monophosphate pathway metabolite regulates short- and long-term control of lipogenesis.''; PubMed Europe PMC Scholia
  130. Arbuckle MI, Kane S, Porter LM, Seatter MJ, Gould GW.; ''Structure-function analysis of liver-type (GLUT2) and brain-type (GLUT3) glucose transporters: expression of chimeric transporters in Xenopus oocytes suggests an important role for putative transmembrane helix 7 in determining substrate selectivity.''; PubMed Europe PMC Scholia
  131. Nakayama T, Penheiter AR, Penheiter SG, Chini EN, Thompson M, Warner DO, Jones KA.; ''Differential effects of volatile anesthetics on M3 muscarinic receptor coupling to the Galphaq heterotrimeric G protein.''; PubMed Europe PMC Scholia
  132. Kang G, Chepurny OG, Malester B, Rindler MJ, Rehmann H, Bos JL, Schwede F, Coetzee WA, Holz GG.; ''cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells.''; PubMed Europe PMC Scholia
  133. Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, Liu W, Lau J, Cherezov V, Katritch V, Wang MW, Stevens RC.; ''Structure of the human glucagon class B G-protein-coupled receptor.''; PubMed Europe PMC Scholia
  134. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  135. Tesmer VM, Kawano T, Shankaranarayanan A, Kozasa T, Tesmer JJ.; ''Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex.''; PubMed Europe PMC Scholia
  136. Fujiwara K, Maekawa F, Yada T.; ''Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet beta-cells: mediation by PLC and L-type Ca2+ channel and link to insulin release.''; PubMed Europe PMC Scholia
  137. Gromada J, Brock B, Schmitz O, Rorsman P.; ''Glucagon-like peptide-1: regulation of insulin secretion and therapeutic potential.''; PubMed Europe PMC Scholia
  138. Kim SJ, Choi WS, Han JS, Warnock G, Fedida D, McIntosh CH.; ''A novel mechanism for the suppression of a voltage-gated potassium channel by glucose-dependent insulinotropic polypeptide: protein kinase A-dependent endocytosis.''; PubMed Europe PMC Scholia
  139. De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F.; ''Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.''; PubMed Europe PMC Scholia
  140. Tsuboi T, Rutter GA.; ''Insulin secretion by 'kiss-and-run' exocytosis in clonal pancreatic islet beta-cells.''; PubMed Europe PMC Scholia
  141. Cummins MM, O'Mullane LM, Barden JA, Cook DI, Poronnik P.; ''Antisense co-suppression of G(alpha)(q) and G(alpha)(11) demonstrates that both isoforms mediate M(3)-receptor-activated Ca(2+) signalling in intact epithelial cells.''; PubMed Europe PMC Scholia
  142. Calle R, Ganesan S, Smallwood JI, Rasmussen H.; ''Glucose-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in isolated rat pancreatic islets.''; PubMed Europe PMC Scholia
  143. Henquin JC, Ishiyama N, Nenquin M, Ravier MA, Jonas JC.; ''Signals and pools underlying biphasic insulin secretion.''; PubMed Europe PMC Scholia
  144. Yamamoto H, Matsumura T, Kugiyama K, Oishi Y, Ogata N, Yasue H, Miyamoto E.; ''The antibody specific for myristoylated alanine-rich C kinase substrate phosphorylated by protein kinase C: activation of protein kinase C in smooth muscle cells in human coronary arteries.''; PubMed Europe PMC Scholia
  145. Runge S, Thøgersen H, Madsen K, Lau J, Rudolph R.; ''Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.''; PubMed Europe PMC Scholia
  146. Trümper J, Ross D, Jahr H, Brendel MD, Göke R, Hörsch D.; ''The Rap-B-Raf signalling pathway is activated by glucose and glucagon-like peptide-1 in human islet cells.''; PubMed Europe PMC Scholia
  147. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M.; ''Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.''; PubMed Europe PMC Scholia
  148. Tarasov AI, Nicolson TJ, Riveline JP, Taneja TK, Baldwin SA, Baldwin JM, Charpentier G, Gautier JF, Froguel P, Vaxillaire M, Rutter GA.; ''A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults.''; PubMed Europe PMC Scholia
  149. Orskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ.; ''Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans.''; PubMed Europe PMC Scholia
  150. MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AM, Light PE, Wheeler MB.; ''The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion.''; PubMed Europe PMC Scholia
  151. Cheng H, Straub SG, Sharp GW.; ''Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE2.''; PubMed Europe PMC Scholia
  152. Wittpoth C, Scholich K, Yigzaw Y, Stringfield TM, Patel TB.; ''Regions on adenylyl cyclase that are necessary for inhibition of activity by beta gamma and G(ialpha) subunits of heterotrimeric G proteins.''; PubMed Europe PMC Scholia
  153. Barg S, Rorsman P.; ''Insulin secretion: a high-affinity Ca2+ sensor after all?''; PubMed Europe PMC Scholia
  154. Verhoeven NM, Huck JH, Roos B, Struys EA, Salomons GS, Douwes AC, van der Knaap MS, Jakobs C.; ''Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway.''; PubMed Europe PMC Scholia
  155. Zhao Y, Fang Q, Straub SG, Sharp GW.; ''Both G i and G o heterotrimeric G proteins are required to exert the full effect of norepinephrine on the beta-cell K ATP channel.''; PubMed Europe PMC Scholia
  156. Yang SN, Berggren PO.; ''The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology.''; PubMed Europe PMC Scholia
  157. Ma L, Sham YY, Walters KJ, Towle HC.; ''A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription.''; PubMed Europe PMC Scholia
  158. Jiang G, Zhang BB.; ''Glucagon and regulation of glucose metabolism.''; PubMed Europe PMC Scholia
  159. Kotarsky K, Nilsson NE, Flodgren E, Owman C, Olde B.; ''A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.''; PubMed Europe PMC Scholia
  160. Hamming KS, Soliman D, Matemisz LC, Niazi O, Lang Y, Gloyn AL, Light PE.; ''Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel.''; PubMed Europe PMC Scholia
  161. Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J.; ''A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo.''; PubMed Europe PMC Scholia
  162. Doyle ME, Egan JM.; ''Mechanisms of action of glucagon-like peptide 1 in the pancreas.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114967view16:49, 25 January 2021ReactomeTeamReactome version 75
113411view11:48, 2 November 2020ReactomeTeamReactome version 74
112613view15:59, 9 October 2020ReactomeTeamReactome version 73
101529view11:39, 1 November 2018ReactomeTeamreactome version 66
101064view21:21, 31 October 2018ReactomeTeamreactome version 65
100595view19:56, 31 October 2018ReactomeTeamreactome version 64
100144view16:41, 31 October 2018ReactomeTeamreactome version 63
99694view15:10, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99282view12:46, 31 October 2018ReactomeTeamreactome version 62
93853view13:41, 16 August 2017ReactomeTeamreactome version 61
93414view11:23, 9 August 2017ReactomeTeamreactome version 61
86502view09:19, 11 July 2016ReactomeTeamreactome version 56
83173view10:17, 18 November 2015ReactomeTeamVersion54
81543view13:05, 21 August 2015ReactomeTeamVersion53
77011view08:30, 17 July 2014ReactomeTeamFixed remaining interactions
76716view12:08, 16 July 2014ReactomeTeamFixed remaining interactions
76042view10:10, 11 June 2014ReactomeTeamRe-fixing comment source
75751view11:24, 10 June 2014ReactomeTeamReactome 48 Update
75101view14:05, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74748view08:49, 30 April 2014ReactomeTeamReactome46
72912view15:20, 14 December 2013EgonwFixed the Uniprot-TrEMBL data sources.
69896view19:21, 11 July 2013MaintBotupdated to 2013 schema
44859view09:54, 6 October 2011MartijnVanIerselOntology Term : 'energy metabolic pathway' added !
42162view23:28, 4 March 2011MaintBotModified categories
42052view21:53, 4 March 2011MaintBotAutomatic update
39857view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,2-

Diacylglycerol

Unknown17815 (ChEBI)
1-Phosphatidyl-

D-myo-inositol 4,5-bisphosphate

Unknown18348 (ChEBI)
1D-myo-Inositol

1,4,5-trisphosphate

Metabolite16595 (ChEBI)
3',5'-Cyclic

AMP

Metabolite17489 (ChEBI)
ACC ProteinREACT_11654 (Reactome)
ADP Metabolite16761 (ChEBI)
ADP/ATP

translocase dimer

ComplexREACT_9306 (Reactome)
AGPAT1 ProteinQ99943 (UniProt)
AMP Metabolite16027 (ChEBI)
AMPK

heterotrimer (inactive)

ComplexREACT_3733 (Reactome)
AMPK

heterotrimer: AMP

ComplexREACT_4802 (Reactome)
ATP Metabolite15422 (ChEBI)
Activated

AMPK heterotrimer

ComplexREACT_5306 (Reactome)
Adenylate

Cyclase V or VI

ProteinREACT_20885 (Reactome)
Adenylate

cyclase (Mg2+ cofactor)

ComplexREACT_17689 (Reactome)
Adenylate cyclase

type V or VI: G- protein beta gamma Complex

ComplexREACT_18486 (Reactome)
Adenylate cyclase:

G-protein alpha (s): GTP Complex

ComplexREACT_19025 (Reactome)
Adenylyl cyclase

(pancreatic beta cell)

ProteinREACT_20747 (Reactome)
Adrenaline and

Noradrenaline

MetaboliteREACT_19090 (Reactome)
Adrenaline/Noradrenalin

e:Alpha-2A/2C Adrenergic Receptor Complex

ComplexREACT_18594 (Reactome)
Alpha-2A/2C

Adrenergic Receptors

ProteinREACT_18657 (Reactome)
C Peptide ProteinP01308 (UniProt)
Ca-

channel (closed)

ComplexREACT_18712 (Reactome)
Ca-

channel (open)

ComplexREACT_18978 (Reactome)
Calcium Metabolite29108 (ChEBI)
ChREBP

protein

ProteinQ9NP71 (UniProt)
ChREBP:

MLX

ComplexREACT_2382 (Reactome)
Core SNARE

Complex

ComplexREACT_16105 (Reactome)
D-Erythrose 4-

phosphate

Metabolite16897 (ChEBI)
D-Fructose 6-

phosphate

Metabolite15946 (ChEBI)
D-Glyceraldehyde

3-phosphate

Metabolite29052 (ChEBI)
D-Xylulose 5-

phosphate

Metabolite16332 (ChEBI)
D-ribose 5-

phosphate

Metabolite17797 (ChEBI)
Dipeptidyl

Peptidase 4

UnknownREACT_24264 (Reactome)
Epac1 ProteinREACT_19050 (Reactome)
Epac1:cAMP

Complex

ComplexREACT_18906 (Reactome)
Epac2 ProteinREACT_18767 (Reactome)
Epac2:cAMP

Complex

ComplexREACT_18747 (Reactome)
Fatty

acids

UnknownREACT_3744 (Reactome)
Fatty acid

synthase

ProteinP49327 (UniProt)
Free fatty acid

receptor 1

ProteinO14842 (UniProt)
Free fatty acid

receptor 1:fatty acid complex

ComplexREACT_19781 (Reactome) The Free fatty acid receptor 1 (FFAR1 or GPR40) is located on pancreatic beta cells and binds to medium and long chain fatty acids (fatty acids having more than 12 carbon groups). FFAR1 is a G-protein coupled receptor that is coupled to Gq.
G beta:G

gamma Complex

ComplexREACT_18681 (Reactome)
G(q) alpha:

GTP: G beta: G gamma Complex (pancreatic beta cell)

ComplexREACT_18484 (Reactome)
G(q) alpha:

GTP Complex (pancreatic beta cell)

ComplexREACT_18564 (Reactome)
G(q):GDP: G beta:

G gamma Complex (pancreatic beta cell)

ComplexREACT_18540 (Reactome)
G-beta:G-

gamma dimer

ComplexREACT_3447 (Reactome)
G-protein

alpha (s):GTP

ComplexREACT_5470 (Reactome)
G-protein

alpha i/o:GTP Complex

ComplexREACT_18504 (Reactome)
G-protein

beta gamma Complex (candidates)

ComplexREACT_18827 (Reactome)
G-protein i/o

alpha:GDP:G- protein beta:G- protein gamma Complex

ComplexREACT_18744 (Reactome)
G-protein i/o

alpha:GTP:G- protein beta:G- protein gamma Complex

ComplexREACT_18596 (Reactome)
G-protein with

G(s) alpha: GDP

ComplexREACT_5026 (Reactome)
GDP Metabolite17552 (ChEBI)
GLP-1: GLP-1R:

Heterotrimeric G (s): GDP Complex

ComplexREACT_18821 (Reactome)
GLP-1: GLP-1R:

Heterotrimeric G (s): GTP Complex

ComplexREACT_18812 (Reactome)
GLP-1R:

Heterotrimeric G (s): GDP Complex

ComplexREACT_18624 (Reactome)
GLUT1 and

GLUT2 (Pancreatic Beta Cell)

ComplexREACT_21462 (Reactome) Human pancreatic beta cells contain GLUT1 and GLUT2 transporters, with GLUT1 predominant. Rodent beta cells predominantly contain GLUT2, which may account for differences observed in the toxicity of streptozotocin.
GPR119:Fatty Acid

Complex

ComplexREACT_24051 (Reactome)
GPR120: Fatty Acid

Complex

ComplexREACT_21753 (Reactome)
GTP Metabolite15996 (ChEBI)
Gastrin-releasing

peptide

ProteinP07492 (UniProt)
Glucagon ProteinP01275 (UniProt)
Glucagon

receptor (GCGR)

ProteinP47871 (UniProt)
Glucagon-like

Peptide-1

UnknownREACT_24372 (Reactome)
Glucagon-like

Peptide-1

ProteinREACT_24529 (Reactome)
Glucagon-like

Peptide-1 (Cleaved at N-terminus)

ProteinREACT_24381 (Reactome)
Glucagon:

GCGR

ComplexREACT_3602 (Reactome)
Glucose-

dependent Insulinotropic Polypeptide

ProteinP09681 (UniProt)
Glucose-

dependent Insulinotropic Polypeptide (Cleaved at N- terminus)

ProteinP09681 (UniProt)
Gs-

activated adenylate cyclase

ComplexREACT_2537 (Reactome)
Gustducin Complex

(alpha, beta, gamma subunits)

ComplexREACT_24604 (Reactome)
H2O Metabolite15377 (ChEBI)
Heterotrimeric

G-alpha(s): GTP:G-beta: G- gamma Complex

ComplexREACT_18711 (Reactome)
Homeobox

protein CDX- 2

ProteinQ99626 (UniProt)
IP3 receptor

homotetramer

ComplexREACT_12247 (Reactome)
IP3 receptor:

IP3 complex

ComplexREACT_12249 (Reactome)
Inactive PP2A-

ABdeltaC complex

ComplexREACT_4092 (Reactome)
Insulin gene enhancer

protein ISL-1

ProteinP61371 (UniProt)
Insulin-Zinc-

Calcium Complex

ComplexREACT_15636 (Reactome)
Insulin:Zinc:Calcium

Complex in docked granule

ComplexREACT_17297 (Reactome)
Inward

Rectifying Potassium Channel (closed)

ComplexREACT_18063 (Reactome)
Inward

Rectifying Potassium Channel (open)

ComplexREACT_17204 (Reactome)
LKB-1 ProteinQ15831 (UniProt)
Leptin ProteinP41159 (UniProt)
Ligands of

FFAR1 (GPR40)

MetaboliteREACT_20176 (Reactome)
MARCKS ProteinP29966 (UniProt)
MLX

protein

ProteinQ9UH92 (UniProt)
Muscarinic

Acetylcholine Receptor M3

ProteinP20309 (UniProt)
Muscarinic

Acetylcholine Receptor M3: Acetylcholine Complex

ComplexREACT_18706 (Reactome)
O-acetylcholine Metabolite15355 (ChEBI)
Orthophosp

hate

Metabolite18367 (ChEBI)
PAX6

isoform 1

ProteinP26367-1 (UniProt)
PC1/3 ProteinP29120 (UniProt)
PFKFB1

dimer

ComplexREACT_2587 (Reactome)
PKA

tetramer

ComplexREACT_5749 (Reactome)
PKA catalytic

subunit

ProteinREACT_3031 (Reactome)
PKA:AKAP79:

IQGAP1 Complex

ComplexREACT_18813 (Reactome)
PP2A-

ABdeltaC complex

ComplexREACT_2369 (Reactome)
PP2A-

ABdeltaC complex

ComplexREACT_5648 (Reactome)
Phospholipase C

Beta (pancreatic beta cell)

ProteinREACT_18548 (Reactome) Pancreatic beta cells contain PLC Beta 1, PLC Beta 2, and PLC Beta 3. It is unknown which PLC or combination of PLC's are activated in response to G(q).
Phospholipase C

Beta: G(q) Complex

ComplexREACT_18449 (Reactome)
Phosphorylated

MARCKS

ProteinP29966 (UniProt)
Potassium

Channel, closed (pancreatic beta cell)

UnknownREACT_21231 (Reactome)
Potassium

Channel, open (pancreatic beta cell)

UnknownREACT_20980 (Reactome)
Potassium

voltage-gated channels (beta cell, closed)

ProteinREACT_18467 (Reactome) Human pancreatic beta cells contain Kv2.1, Kv3.2, Kv6.2, and Kv9.3 voltage gated potassium channels. The channels are closed in a resting beta and channels open in response to depolarization. Open channels counteract the effect of closed ATP-gated potassium channels and thereby end stimulation of insulin secretion .
Potassium

voltage-gated channels (beta cell, open)

ProteinREACT_18949 (Reactome) Human pancreatic beta cells contain Kv2.1, Kv3.2, Kv6.2, and Kv9.3 voltage gated potassium channels. The channels are closed in a resting beta and channels open in response to depolarization. Open channels counteract the effect of closed ATP-gated potassium channels and thereby end stimulation of insulin secretion .
PreproGIP ProteinP09681 (UniProt)
Preproglucagon ProteinP01275 (UniProt)
ProGIP ProteinP09681 (UniProt)
Proglucagon ProteinP01275 (UniProt)
Protein

Kinase A, catalytic subunits

ProteinREACT_2480 (Reactome)
Protein

kinase C, alpha type

ProteinP17252 (UniProt)
Protein Kinase

C, alpha type: Diacylglycerol Complex

ComplexREACT_18539 (Reactome)
Pyruvate kinase,

R isozyme

ProteinP30613-1 (UniProt)
Rap1-

GDP

ComplexREACT_15771 (Reactome)
Rap1-

GTP

ComplexREACT_16044 (Reactome)
SNAP-25 ProteinREACT_18216 (Reactome)
SNARE Complex ComplexREACT_15643 (Reactome)
SUR1 ProteinQ09428 (UniProt)
Sedoheptulose

7-phosphate

Metabolite15721 (ChEBI)
Signal Peptidase

Complex

ComplexREACT_15945 (Reactome)
Synaptotagmin

V

ProteinO00445 (UniProt)
Syntaxin-1A-

Unc18-1 Complex

ComplexREACT_16057 (Reactome)
Transcription factor

GATA-4

ProteinP43694 (UniProt)
Unc18-1 ProteinREACT_16070 (Reactome)
VAMP2/Synapto

brevin2

ProteinP63027 (UniProt)
Voltage-gated

Calcium Channels (pancreatic beta cell)

ComplexREACT_17848 (Reactome)
Voltage-gated

Calcium Channels Type Cav1 (closed)

ComplexREACT_19083 (Reactome)
Voltage-gated

Calcium Channels Type Cav1 (open)

ComplexREACT_18725 (Reactome)
alpha-D-

glucose

Metabolite17925 (ChEBI)
cAMP:PKA

regulatory subunit

ComplexREACT_4571 (Reactome)
cAMP:PKA:

AKAP79: IQGAP1 Complex

ComplexREACT_18785 (Reactome)
citrate lyase

monomer

ProteinP53396 (UniProt)
hTCF-4:Beta-

catenin

ComplexREACT_24275 (Reactome)
mature

GLP-1

ProteinREACT_19088 (Reactome)
pChREBP

(Thr 666)

ProteinQ9NP71 (UniProt)
pChREBP (Ser

196, Thr 666)

ProteinQ9NP71 (UniProt)
pChREBP (Thr

666)

ProteinQ9NP71 (UniProt)
pChREBP(Ser

568)

ProteinQ9NP71 (UniProt)
phosphoPFKFB

1 dimer

ComplexREACT_3400 (Reactome)
pyrophosp

hate

Metabolite29888 (ChEBI)
transaldolase 1 ProteinP37837 (UniProt)
transketolase

dimer

ComplexREACT_3387 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1831"
Personal tools