ArticleDisease models & mechanisms2016
Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Article
- Alternative RNA Splicing in Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Lipid mediators of insulin signaling in diabetic kidney disease.American journal of physiology. Renal physiology · 2019Review
- The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer.Cells · 2019Review
- Cytohesin-3 is required for full insulin receptor signaling and controls body weight via lipid excretion.Scientific reports · 2019Article
- Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity.Disease models & mechanisms · 2019Article
- Effect ofSaudi journal of biological sciences · 2019Article
- Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue.Frontiers in physiology · 2018Article
- Biochemical and cellular properties of insulin receptor signalling.Nature reviews. Molecular cell biology · 2018Review
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat.Disease models & mechanisms · 2017Article
- Expression of insulin receptor (IR) A and B isoforms, IGF-IR, and IR/IGF-IR hybrid receptors in vascular smooth muscle cells and their role in cell migration in atherosclerosis.Cardiovascular diabetology · 2016Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte--specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus.
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