How do different receptor types contribute to insulin resistance?
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Different receptor types, such as the insulin receptor isoforms IR-A and IR-B, play a crucial role in contributing to insulin resistance. Mutations in the tyrosine kinase domain of the insulin receptor gene (INSR) can impair receptor function, leading to insulin resistance and hyperinsulinemia. In conditions like myotonic dystrophy, alterations in downstream insulin signaling pathways, including Akt/PKB and ERK1/2, contribute to insulin resistance independent of INSR splicing abnormalities. Furthermore, dynamic clusters of the insulin receptor in hepatocytes and adipocytes are affected in insulin-resistant cells, with reduced accumulation and altered behavior, which can be rescued by metformin treatment. Defects in the INSR gene, such as missense mutations, can also lead to congenital insulin resistance syndromes like leprechaunism, highlighting the critical role of receptor mutations in insulin resistance.
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6 Citations | Primary insulin receptor defects, such as INSR mutations (e.g., Gly1146Arg, Ser98Arg), lead to insulin resistance by disrupting protein functions, highlighting the crucial role of insulin receptor abnormalities in insulin resistance. |
| The dynamic clustering of insulin receptor is disrupted in insulin resistance, affecting its signaling. This altered behavior contributes to impaired metabolic control in conditions like type 2 diabetes. | |
| The insulin receptor (INSR) mediates insulin's actions on glucose homeostasis. Mutations in the tyrosine kinase domain can lead to insulin resistance, potentially exacerbated by HCV infection-induced liver complications. | |
34 Citations | Post-receptor abnormalities, alongside altered insulin receptor splicing, contribute to insulin resistance in myotonic dystrophy type 1 and type 2 skeletal muscle, impacting downstream insulin pathway signaling and glucose uptake. |
07 Dec 2022 | Insulin receptor isoforms, IR-A and IR-B, with varying ligand affinities, may influence insulin resistance by altering signaling cascades, potentially impacting metabolic disorders like obesity and type 2 diabetes. |
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