ArticleDiabetologia2007
Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice.
Article in Diabetologia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes.Molecular metabolism · 2021Article
- Gsα-dependent signaling is required for postnatal establishment of a functional β-cell mass.Molecular metabolism · 2021Article
- Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2020Review
- The beneficial effects of a muscarinic agonist on pancreatic β-cells.Scientific reports · 2019Article
- β-Cell Fate in Human Insulin Resistance and Type 2 Diabetes: A Perspective on Islet Plasticity.Diabetes · 2019Review
- Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity.Molecular metabolism · 2019Article
- Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass.Diabetologia · 2019Article
- Neuronatin regulates pancreatic β cell insulin content and secretion.The Journal of clinical investigation · 2018Article
- The PI3K/AKT pathway in obesity and type 2 diabetes.International journal of biological sciences · 2018Review
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion.The Journal of clinical investigation · 2017Article
- Glucose Induces Mouse β-Cell Proliferation via IRS2, MTOR, and Cyclin D2 but Not the Insulin Receptor.Diabetes · 2016Article
- Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.The Journal of biological chemistry · 2015Article
- DOC2 isoforms play dual roles in insulin secretion and insulin-stimulated glucose uptake.Diabetologia · 2014Article
- The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis.Mammalian genome : official journal of the International Mammalian Genome Society · 2014Review
- Review
- The regulation of pre- and post-maturational plasticity of mammalian islet cell mass.Diabetologia · 2014Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisInsulin signalling pathways regulate pancreatic beta cell function. Conditional gene targeting using the Cre/loxP system has demonstrated that mice lacking insulin receptor substrate 2 (IRS2) in the beta cell have reduced beta cell mass. However, these studies have been complicated by hypothalamic deletion when the RIPCre (B6.Cg-tg(Ins2-cre)25Mgn/J) transgenic mouse (expressing Cre recombinase under the control of the rat insulin II promoter) is used to delete floxed alleles in insulin-expressing cells. These features have led to marked insulin resistance making the beta cell-autonomous role of IRS2 difficult to determine. To establish the effect of deleting Irs2 only in the pancreas, we generated PIrs2KO mice in which Cre recombinase expression was driven by the promoter of the pancreatic and duodenal homeobox factor 1 (Pdx1, also known as Ipf1) gene. MATERIALS AND
methodsIn vivo glucose homeostasis was examined in PIrs2KO mice using glucose tolerance and glucose-stimulated insulin secretion tests. Endocrine cell mass was determined by morphometric analysis. Islet function was examined in static cultures and by performing calcium imaging in Fluo3am-loaded beta cells. Islet gene expression was determined by RT-PCR.
resultsThe PIrs2KO mice displayed glucose intolerance and impaired glucose-stimulated insulin secretion in vivo. Pancreatic insulin and glucagon content and beta and alpha cell mass were reduced. Glucose-stimulated insulin secretion and calcium mobilisation were attenuated in PIrs2KO islets. Expression of the Glut2 gene (also known as Slc2a2) was also reduced in PIrs2KO mice. CONCLUSIONS/
interpretationThese studies suggest that IRS2-dependent signalling in pancreatic islets is required not only for the maintenance of normal beta and alpha cell mass but is also involved in the regulation of insulin secretion.
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