Year: 2009
Type: article
Abstract: Insulin/IGF-I signaling regulates the metabolism of most mammalian tissues including pancreatic islets. To dissect the mechanisms linking insulin signaling with mitochondrial function, we first identified a mitochondria-tethering complex in beta-cells that included glucokinase (GK), and the pro-apoptotic protein, BAD(S). Mitochondria isolated from beta-cells derived from beta-cell specific insulin receptor knockout (betaIRKO) mice exhibited reduced BAD(S), GK and protein kinase A in the complex, and attenuated function. Similar alterations were evident in islets from patients with type 2 diabetes. Decreased mitochondrial GK activity in betaIRKOs could be explained, in part, by reduced expression and altered phosphorylation of BAD(S). The elevated phosphorylation of p70S6K and JNK1 was likely due to compensatory increase in IGF-1 receptor expression. Re-expression of insulin receptors in betaIRKO cells partially restored the stoichiometry of the complex and mitochondrial function. These data indicate that insulin signaling regulates mitochondrial function and have implications for beta-cell dysfunction in type 2 diabetes.
Source: PLoS ONE
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1105102958, Metabolic Regulation of Insulin Secretion, G2345861605, Insulin resistance and cardiac dysfunction in obesity, Metabolic Signal Transduction in Adipocytes, Dissecting the Death Pathway in Islet Beta Cells, G8374322486, Diabetes Research Center, Role of IGF-1 and insulin receptors beta-cell survival, G951333326
OpenAlex ID: W2104864428