Type II diabetes mellitus (Homo sapiens)

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1-4Adipocytokine signaling pathway+ps (serine phosphorylation)Adipocyte, hepatocyte, or skeletal muscle cell Glycation, hexosamine pathway,respiratory chain+py (tyrosine phosphorylation)(hyperglycemia)ROSTransient hyperglycemia hyperinsulinismAdipocytokine signaling pathwayImpaired insulin secretionPrevention of membrane depolarizationDNACa2+ dependentK+Insulin resistanceERKKir6.2P13K PRKCDApoptosisMAFAGlucoseMTORPRKCZTNF alphaINSPDX-1ATPGLUT2VDCCGLUT4GlucoseIRSADIPOQSOCSGKSURF1PyruvateIRSJNKINSRPYKInsulin signalingINSJNKIKKType II diabetesCa2+Pancreatic beta cellFFAObesityObesityMaturity-onsetdiabetes of the young


Description

Insulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Serine/threonine phosphorylation, interaction with SOCS, regulation of the expression, modification of the cellular localization, and degradation represent the molecular mechanisms stimulated by them. Various kinases (ERK, JNK, IKKbeta, PKCzeta, PKCtheta and mTOR) are involved in this process.

The development of type II diabetes requires impaired beta-cell function. Chronic hyperglycemia has been shown to induce multiple defects in beta-cells. Hyperglycemia has been proposed to lead to large amounts of reactive oxygen species (ROS) in beta-cells, with subsequent damage to cellular components including PDX-1. Loss of PDX-1, a critical regulator of insulin promoter activity, has also been proposed as an important mechanism leading to beta-cell dysfunction.

Although there is little doubt as to the importance of genetic factors in type II diabetes, genetic analysis is difficult due to complex interaction among multiple susceptibility genes and between genetic and environmental factors. Genetic studies have therefore given very diverse results. Kir6.2 and IRS are two of the candidate genes. It is known that Kir6.2 and IRS play central roles in insulin secretion and insulin signal transmission, respectively.

Source: KEGG

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

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Ontology Terms

 

Bibliography

  1. Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren PO, Orrenius S; ''Role of apoptosis in pancreatic beta-cell death in diabetes.''; Diabetes, 2001 PubMed Europe PMC Scholia
  2. Henquin JC; ''Triggering and amplifying pathways of regulation of insulin secretion by glucose.''; Diabetes, 2000 PubMed Europe PMC Scholia
  3. Kaneto H, Matsuoka TA, Nakatani Y, Kawamori D, Miyatsuka T, Matsuhisa M, Yamasaki Y; ''Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes.''; J Mol Med (Berl), 2005 PubMed Europe PMC Scholia
  4. Gual P, Le Marchand-Brustel Y, Tanti JF; ''Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.''; Biochimie, 2005 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
128477view00:12, 5 February 2024EweitzFix gene names, refine more vertical placements
128476view00:06, 5 February 2024EweitzRefine vertical placements
128475view23:53, 4 February 2024EweitzUpgrade another disease, fix graphics overlap
128474view22:59, 4 February 2024EweitzUpgrade disease / medical condition nodes
128473view22:50, 4 February 2024EweitzRefine graphics
128472view22:41, 4 February 2024EweitzFormalize cells
128471view22:24, 4 February 2024EweitzOntology Term : 'hepatocyte' added !
128470view22:24, 4 February 2024EweitzOntology Term : 'cell of skeletal muscle' added !
128469view22:23, 4 February 2024EweitzOntology Term : 'adipocyte' added !
128468view22:22, 4 February 2024EweitzEconomize layout
128467view22:10, 4 February 2024EweitzEconomize layout
128466view21:57, 4 February 2024EweitzFix typos, standardize case
126398view15:32, 26 April 2023EgonwLicense is CCZero
122869view08:09, 27 May 2022EgonwMade a pathway clickable
111210view21:19, 24 July 2020Ssd1805Ontology Term : 'diabetes mellitus' added !
111209view21:15, 24 July 2020Ssd1805Ontology Term : 'DOID:9352' removed !
108356view19:37, 11 December 2019KhanspersOntology Term : 'disease pathway' added !
106156view12:05, 16 August 2019MaintBotHMDB identifier normalization
105849view23:15, 15 August 2019KhanspersModified description
94959view10:10, 20 October 2017DeSlAdded lit. references
94958view09:44, 20 October 2017DeSlConnected all lines that I could
81779view19:00, 26 August 2015KhanspersModified description
81778view18:58, 26 August 2015KhanspersModified description
72094view21:35, 24 October 2013Mkutmonupdated datasource for "Apoptosis"
67730view11:55, 26 June 2013DdiglesOntology Term : 'type 2 diabetes mellitus pathway' added !
63481view18:29, 10 May 2013AlexanderPicoFixed Xref for PYK
63274view07:16, 9 May 2013EveloPeriodical save, work in progress
59217view20:13, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45036view18:50, 6 October 2011KhanspersOntology Term : 'pancreatic beta cell' added !
45034view18:49, 6 October 2011KhanspersOntology Term : 'hyperglycemia' added !
45032view18:47, 6 October 2011KhanspersOntology Term : 'DOID:9351' removed !
45031view18:47, 6 October 2011KhanspersOntology Term : 'type 2 diabetes mellitus' added !
45030view18:47, 6 October 2011KhanspersOntology Term : 'Diabetes' added !
41223view23:45, 1 March 2011MaintBotRemoved redundant pathway information and comments
38693view18:35, 23 September 2010KhanspersChanged layout, connected nodes, added metabolites, added pathway links, fixed arrows
38692view18:26, 23 September 2010KhanspersPeriodical save, work in progress
38690view18:25, 23 September 2010Khanspersperiodical save
38312view22:45, 31 August 2010KhanspersChanged OrganA to Oval
38145view19:00, 17 August 2010KhanspersModified categories
37822view10:08, 6 July 2010AnkuPeriodical save, work in progress
37821view09:55, 6 July 2010AnkuPeriodical save, work in progress
37820view09:44, 6 July 2010AnkuPeriodical save, work in progress
37819view09:34, 6 July 2010AnkuPeriodical save, work in progress
37813view15:05, 5 July 2010AnkuModified description
37812view15:04, 5 July 2010Ankudiabetes type II
37811view14:55, 5 July 2010AnkuPeriodical save, work in progress
37810view14:33, 5 July 2010AnkuPeriodical save, work in progress
37809view14:23, 5 July 2010AnkuPeriodical save, work in progress
37808view14:13, 5 July 2010AnkuPeriodical save, work in progress
37807view14:02, 5 July 2010AnkuPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
PRKCDGeneProductENSG00000163932 (Ensembl)
ADIPOQGeneProductENSG00000181092 (Ensembl)
ATPMetaboliteHMDB0000538 (HMDB)
ApoptosisPathwayWP254 (WikiPathways)
Ca2+MetaboliteHMDB0000464 (HMDB)
ERKGeneProductENSG00000100030 (Ensembl)
FFAMetabolite17234 (ChEBI)
GKGeneProductENSG00000198814 (Ensembl)
GLUT2GeneProductENSG00000163581 (Ensembl)
GLUT4GeneProductENSG00000181856 (Ensembl)
GlucoseMetabolite17234 (ChEBI)
GlucoseMetaboliteHMDB0000122 (HMDB)
IKKGeneProductENSG00000104365 (Ensembl)
INSGeneProductENSG00000129965 (Ensembl)
INSRGeneProductENSG00000171105 (Ensembl)
IRSGeneProductENSG00000169047 (Ensembl)
Insulin signalingPathwayWP481 (WikiPathways)
JNKGeneProductENSG00000107643 (Ensembl)
Kir6.2GeneProductENSG00000187486 (Ensembl)
MAFAGeneProductENSG00000182759 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
Maturity-onset diabetes of the youngQ663041 (Wikidata)
ObesityQ12174 (Wikidata)
P13KGeneProductENSG00000141506 (Ensembl)
PDX-1GeneProductENSG00000139515 (Ensembl)
PRKCZGeneProductENSG00000067606 (Ensembl)
PYKGeneProductENSG00000044446 (Ensembl)
PyruvateMetaboliteHMDB0000243 (HMDB)
SOCSGeneProductENSG00000180008 (Ensembl)
SURF1GeneProductENSG00000148290 (Ensembl)
TNF alphaGeneProductENSG00000232810 (Ensembl)
Type II diabetesQ3025883 (Wikidata)
VDCCGeneProductENSG00000141837 (Ensembl)

Annotated Interactions

No annotated interactions

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