ArticleThe Journal of clinical endocrinology and metabolism2013
Joint effect of insulin signaling genes on insulin secretion and glucose homeostasis.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus.Endocrine · 2016Pooled it
- Flavonoids fromJournal of enzyme inhibition and medicinal chemistry · 2026Article
- ADisease models & mechanisms · 2017Article
- Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells.PloS one · 2017Article
- Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes.Atherosclerosis · 2015Article
- Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus.American journal of human genetics · 2015Article
- Joint effect of insulin signaling genes on all-cause mortality.Atherosclerosis · 2014Article
- Drosophila tribbles antagonizes insulin signaling-mediated growth and metabolism via interactions with Akt kinase.PloS one · 2014Article
- The IRS1 G972R polymorphism and glomerular filtration rate in patients with type 2 diabetes of European ancestry.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013Article
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 2 countries.
Funding
Abstract
contextReduced insulin signaling in insulin secreting β-cells causes defective insulin secretion and hyperglycemia in mice.
objectiveWe investigated whether functional polymorphisms affecting insulin signaling (ie, ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; and TRIB3 Q84R, rs2295490) exert a joint effect on insulin secretion and abnormal glucose homeostasis (AGH).
designInsulin secretion was evaluated by 1) the disposition index (DI) from an oral glucose tolerance test (OGTT) in 829 individuals; 2) insulin secretion stimulation index (SI) in islets from nondiabetic donors after glucose (n = 92) or glibenclamide (n = 89) stimulation. AGH (including impaired fasting glucose and/or impaired glucose tolerance or type 2 diabetes; T2D) was evaluated in case-control studies from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) Consortium (n = 6607).
resultsGenotype risk score, obtained by totaling individual weighted risk allele effects, was associated with the following: 1) DI (P = .005); 2) glucose and glibenclamide SI (P = .046 and P = .009); or 3) AGH (odds ratio 1.08, 95% confidence interval 1.03-1.13; P = .001). We observed an inverse relationship between genetic effect and age at AGH onset, as indicated by a linear correlation between AGH-genotype risk score odds ratios and age-at-diagnosis cutoffs (R(2) = 0.80, P < .001).
conclusionsFunctional polymorphisms affecting insulin signaling exert a joint effect on both in vivo and in vitro insulin secretion as well as on early-onset AGH. Our data provide further evidence that abnormal insulin signaling reduces β-cell function and impairs glucose homeostasis.
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