Growth factors and hormones in beta cell proliferation (Homo sapiens)

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6123259137127442144661016146128, 11, 1241098791114961432712Beta cellPref-1B-RafPI3KIGF-1FOXO1VEGFR-1ProliferationEZH2TRsRab43IRPref-1RCyclin APDGFaSmad7Cyclin DP16ink4aPdx1AKT1IGF-1RT3PLGFInsulinNFATERK 1Ca2+K-RasTGFB1TGFB1RT4CRTC2Rasf1aPDGFR-a4, 676715624104CaM710541142cMycCDK2CDK4FOXM1ERK 2T3AKT2AKT3


Description

Several growth factors and hormones interact with particular beta-cell receptors to start intracellular signaling pathways that encourage cell division and growth. Hormones including prolactin (PRL), thyroid hormone (TH), growth hormone (GH), glucagon-like peptide-1 (GLP-1), insulin-like growth factor-1 (IGF-1), and others have been closely linked. The modulation of B-cell proliferation has been linked to growth factors such as IGF-1, members of the epidermal growth factor (EGF) family, nerve growth factor (NGF), members of the transforming growth factor (TGF)-superfamily, placental growth factor (PLGF), and their corresponding receptors. This pathway provides information on how these various factors are realized. The figure is based on Jiang et al. (2018, doi: 10.3892/etm.2018.6603).

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Bibliography

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  1. Blum B, Roose AN, Barrandon O, Maehr R, Arvanites AC, Davidow LS, Davis JC, Peterson QP, Rubin LL, Melton DA; ''Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway.''; Elife, 2014 PubMed Europe PMC Scholia
  2. Kim TK, Lee JS, Jung HS, Ha TK, Kim SM, Han N, Lee EJ, Kim TN, Kwon MJ, Lee SH, Kim MK, Rhee BD, Park JH; ''Triiodothyronine induces proliferation of pancreatic β-cells through the MAPK/ERK pathway.''; Exp Clin Endocrinol Diabetes, 2014 PubMed Europe PMC Scholia
  3. Wang C, Chen X, Ding X, He Y, Gu C, Zhou L; ''Exendin-4 Promotes Beta Cell Proliferation via PI3k/Akt Signalling Pathway.''; Cell Physiol Biochem, 2015 PubMed Europe PMC Scholia
  4. Chen H, Gu X., Liu Y., Wang J., Wirt SE, Bottino R., Schorle H., Sage J., Kim SK.; ''PDGF signalling controls age-dependent proliferation in pancreatic β-cells''; nature10502, 2011 PubMed Europe PMC Scholia
  5. Xiao X, Gaffar I, Guo P, Wiersch J, Fischbach S, Peirish L, Song Z, El-Gohary Y, Prasadan K, Shiota C, Gittes GK; ''M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7.''; Proc Natl Acad Sci U S A, 2014 PubMed Europe PMC Scholia
  6. Jiang WJ, Peng YC, Yang KM; ''Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes.''; Exp Ther Med, 2018 PubMed Europe PMC Scholia
  7. Chamberlain CE, Scheel DW, McGlynn K, Kim H, Miyatsuka T, Wang J, Nguyen V, Zhao S, Mavropoulos A, Abraham AG, O'Neill E, Ku GM, Cobb MH, Martin GR, German MS; ''Menin determines K-RAS proliferative outputs in endocrine cells.''; J Clin Invest, 2014 PubMed Europe PMC Scholia
  8. Demozay D, Tsunekawa S, Briaud I, Shah R, Rhodes CJ; ''Specific glucose-induced control of insulin receptor substrate-2 expression is mediated via Ca2+-dependent calcineurin/NFAT signaling in primary pancreatic islet β-cells.''; Diabetes, 2011 PubMed Europe PMC Scholia
  9. Rhee M, Lee SH, Kim JW, Ham DS, Park HS, Yang HK, Shin JY, Cho JH, Kim YB, Youn BS, Sul HS, Yoon KH; ''Preadipocyte factor 1 induces pancreatic ductal cell differentiation into insulin-producing cells.''; Sci Rep, 2016 PubMed Europe PMC Scholia
  10. Wang H, Gambosova K, Cooper ZA, Holloway MP, Kassai A, Izquierdo D, Cleveland K, Boney CM, Altura RA; ''EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells.''; BMC Mol Biol, 2010 PubMed Europe PMC Scholia
  11. Park YJ, Yoo SA, Kim M, Kim WU; ''The Role of Calcium-Calcineurin-NFAT Signaling Pathway in Health and Autoimmune Diseases.''; Front Immunol, 2020 PubMed Europe PMC Scholia
  12. Goodyer WR, Gu X, Liu Y, Bottino R, Crabtree GR, Kim SK; ''Neonatal β cell development in mice and humans is regulated by calcineurin/NFAT.''; Dev Cell, 2012 PubMed Europe PMC Scholia
  13. Gao Y, Liao G, Xiang C, Yang X, Cheng X, Ou Y; ''Effects of phycocyanin on INS-1 pancreatic β-cell mediated by PI3K/Akt/FoxO1 signaling pathway.''; Int J Biol Macromol, 2016 PubMed Europe PMC Scholia
  14. Li J, Ying H, Cai G, Guo Q, Chen L; ''Pre-Eclampsia-Associated Reduction in Placental Growth Factor Impaired Beta Cell Proliferation Through PI3k Signalling.''; Cell Physiol Biochem, 2015 PubMed Europe PMC Scholia
  15. Cerf ME, Williams K, Chapman CS, Louw J; ''Compromised beta-cell development and beta-cell dysfunction in weanling offspring from dams maintained on a high-fat diet during gestation.''; Pancreas, 2007 PubMed Europe PMC Scholia
  16. Kaneko K, Ueki K, Takahashi N, Hashimoto S, Okamoto M, Awazawa M, Okazaki Y, Ohsugi M, Inabe K, Umehara T, Yoshida M, Kakei M, Kitamura T, Luo J, Kulkarni RN, Kahn CR, Kasai H, Cantley LC, Kadowaki T; ''Class IA phosphatidylinositol 3-kinase in pancreatic β cells controls insulin secretion by multiple mechanisms.''; Cell Metab, 2010 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
128454view18:44, 4 February 2024EweitzModified title
128453view18:43, 4 February 2024EweitzRefine node alignment
128452view18:41, 4 February 2024EweitzEconomize layout
128451view18:23, 4 February 2024EweitzEconomize node dimensions
127774view20:16, 4 December 2023Khanspersminor layout change
126898view12:01, 30 June 2023Cereno98Missing Reference update
126897view11:53, 30 June 2023Tesic petraAlignment of the data nodes
126896view11:15, 30 June 2023Leyla ÖnderPoliferation - data node
126895view11:09, 30 June 2023Tesic petraAdding the reference to the title section
126894view11:05, 30 June 2023Tesic petraRemovement of the squares on the lines
126893view11:01, 30 June 2023Cereno98Fixing not connected arrows.
126892view10:57, 30 June 2023Cereno98connection error removal
126827view07:49, 26 June 2023Tesic petraModified description
126820view09:53, 25 June 2023EgonwRemoved whitespace from a few datanode labels
126746view17:04, 16 June 2023Cereno98References updated
126745view16:57, 16 June 2023Cereno98reference update
126729view23:09, 15 June 2023Cereno98Modified description
126728view20:58, 15 June 2023Tesic petraModified title
126727view20:18, 15 June 2023Leyla ÖnderReferences
126726view19:02, 15 June 2023Cereno98Reference addition
126712view13:14, 14 June 2023Leyla ÖnderComments on the DataNodes
126711view11:36, 14 June 2023Cereno98gene
126710view11:35, 14 June 2023Cereno98complex
126709view11:34, 14 June 2023Cereno98id
126708view11:34, 14 June 2023Cereno98protein
126707view11:29, 14 June 2023Cereno98Metabolite ID update
126706view11:28, 14 June 2023Cereno98Correction of metabolites
126705view10:44, 14 June 2023Cereno98Modified description
126704view10:43, 14 June 2023Cereno98Modified description
126703view08:37, 14 June 2023Leyla ÖnderOntology Term : 'transforming growth factor-beta superfamily mediated signaling pathway' added !
126702view08:36, 14 June 2023Leyla ÖnderOntology Term : 'Ras family mediated signaling pathway' added !
126701view08:33, 14 June 2023Leyla ÖnderOntology Term : 'calcium/calcium-mediated signaling pathway' added !
126700view08:32, 14 June 2023Leyla ÖnderOntology Term : 'phosphatidylinositol 3-kinase-Akt signaling pathway' added !
126699view08:32, 14 June 2023Leyla ÖnderOntology Term : 'insulin signaling pathway' added !
126698view08:28, 14 June 2023Leyla ÖnderOntology Term : 'type B pancreatic cell' added !
126697view07:30, 14 June 2023Leyla ÖnderNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1GeneProductP31749 (Uniprot-TrEMBL)
AKT2GeneProductP31751 (Uniprot-TrEMBL)
AKT3GeneProductQ9Y243 (Uniprot-TrEMBL)
B-RafGeneProductP15056 (Uniprot-TrEMBL)
CDK2GeneProductP24941 (Uniprot-TrEMBL)
CDK4GeneProductP11802 (Uniprot-TrEMBL)
CRTC2GeneProductQ53ET0 (Uniprot-TrEMBL)
Ca2+Metabolite29108 (ChEBI)
CaMGeneProductUniProt provides different types of Calmodulin proteins. The publication does not state which CaM is involved in the ß-proliferation. While searching for a family identifier with InterPro, no results were retrieved.
Cyclin AGeneProductThere are two types of Cyclin A: A1 and A2. There is no specifcation about which type is important and no InterPro identifiers is found.
Cyclin DGeneProductThere are two types of Cyclin D: D1,D2 and D3. There is no specifcation about which type is important and no InterPro identifiers is found.
ERK 1GeneProductP27361 (Uniprot-TrEMBL)
ERK 2GeneProductP28482 (Uniprot-TrEMBL)
EZH2GeneProductQ75MQ0 (Uniprot-TrEMBL)
FOXM1GeneProductQ08050 (Uniprot-TrEMBL)
FOXO1GeneProductQ12778 (Uniprot-TrEMBL)
IGF-1GeneProductP05019 (Uniprot-TrEMBL)
IGF-1RGeneProductP08069 (Uniprot-TrEMBL) In contrast to the pathway figure, the specific receptor was included as DataNode.
IRGeneProductP06213 (Uniprot-TrEMBL) In contrast to the pathway figure, the specific receptor was included as DataNode.
InsulinGeneProductP01308 (Uniprot-TrEMBL)
K-RasGeneProductP01116 (Uniprot-TrEMBL)
NFATGeneProductIPR008366 (InterPro) The InterPro indentifier for the family was selected, as no specifc protein of the family was stated in the publication.
P16ink4aGeneProductR9S252 (Uniprot-TrEMBL)
PDGFR-aGeneProductA0A387LBM6 (Uniprot-TrEMBL) In contrast to the pathway figure, the specific receptor was included as DataNode.
PDGFaGeneProductP04085 (Uniprot-TrEMBL)
PI3KGeneProductIPR000403 (InterPro) The InterPro indentifier for the family was selected, as no specifc protein of the family was stated in the publication.
PLGFGeneProductP49763 (Uniprot-TrEMBL)
Pdx1GeneProductP52945 (Uniprot-TrEMBL)
Pref-1GeneProductP80370 (Uniprot-TrEMBL) Synonyms: Dlk-1
Pref-1RGeneProductNo identifier was found.
ProliferationQ189101 (Wikidata)
Rab43GeneProductQ86YS6 (Uniprot-TrEMBL)
Rasf1aGeneProductQ9NS23 (Uniprot-TrEMBL)
Smad7GeneProductO15105 (Uniprot-TrEMBL)
T3Metabolite18258 (ChEBI)
T4Metabolite18332 (ChEBI)
TGFB1GeneProductP01137 (Uniprot-TrEMBL)
TGFB1RGeneProductP36897 (Uniprot-TrEMBL)
TRsGeneProductIPR001728 (InterPro)
VEGFR-1GeneProductP17948 (Uniprot-TrEMBL) The pathway figure namesthe receptor for PLGF as PLGF. The UniProt websites states that the receptor for PLGF is VEGFR-1. But the original publication (PMID: 25924650) states VEGFR-1 as receptor.
cMycGeneProductP01106 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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