ArticleDiabetes2020
Muscle-Specific Insulin Receptor Overexpression Protects Mice From Diet-Induced Glucose Intolerance but Leads to Postreceptor Insulin Resistance.
Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Effect of exercise training on skeletal muscle protein expression in relation to insulin sensitivity: Per-protocol analysis of a randomized controlled trial (GO-ACTIWE).Physiological reports · 2021Trial
- Hepatic glutathione depletion ameliorates MASLD through selective protein oxidation and inhibition of lipogenesis.The Journal of clinical investigation · 2026Article
- Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.Brain, behavior, and immunity · 2026Article
- Article
- Multi Targeted Activity of Cocculus hirsutus through Modulation of DPP-IV and PTP-1B Leading to Enhancement of Glucose Uptake and Attenuation of Lipid Accumulation.Applied biochemistry and biotechnology · 2025Article
- Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α.Diabetologia · 2024Article
- Normalization of maternal adiponectin in obese pregnant mice prevents programming of impaired glucose metabolism in adult offspring.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Visceral adiposity, inflammation, and hippocampal function in obesity.Neuropharmacology · 2022Review
- Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- The Roles of the IGF Axis in the Regulation of the Metabolism: Interaction and Difference between Insulin Receptor Signaling and IGF-I Receptor Signaling.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Skeletal muscle insulin resistance is a prominent early feature in the pathogenesis of type 2 diabetes. In attempt to overcome this defect, we generated mice overexpressing insulin receptors (IR) specifically in skeletal muscle (IRMOE). On normal chow, IRMOE mice have body weight similar to that of controls but an increase in lean mass and glycolytic muscle fibers and reduced fat mass. IRMOE mice also show higher basal phosphorylation of IR, IRS-1, and Akt in muscle and improved glucose tolerance compared with controls. When challenged with high-fat diet (HFD), IRMOE mice are protected from diet-induced obesity. This is associated with reduced inflammation in fat and liver, improved glucose tolerance, and improved systemic insulin sensitivity. Surprisingly, however, in both chow and HFD-fed mice, insulin-stimulated Akt phosphorylation is significantly reduced in muscle of IRMOE mice, indicating postreceptor insulin resistance. RNA sequencing reveals downregulation of several postreceptor signaling proteins that contribute to this resistance. Thus, enhancing early insulin signaling in muscle by overexpression of the IR protects mice from diet-induced obesity and its effects on glucose metabolism. However, chronic overstimulation of this pathway leads to postreceptor desensitization, indicating the critical balance between normal signaling and hyperstimulation of the insulin signaling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.