Insulin Signaling Regulates Mitochondrial Function in Pancreatic β-Cells
Date
2009-11-24
Authors
Liu, Siming
Okada, Terumasa
Assmann, Anke
Soto, Jamie
Liew, Chong Wee
Bugger, Heiko
Shirihai, Orian S.
Abel, E. Dale
Kulkarni, Rohit N.
Version
OA Version
Citation
Liu, Siming, Terumasa Okada, Anke Assmann, Jamie Soto, Chong Wee Liew, Heiko Bugger, Orian S. Shirihai, E. Dale Abel, Rohit N. Kulkarni. "Insulin Signaling Regulates Mitochondrial Function in Pancreatic β-Cells" PLoS ONE 4(11): e7983. (2009)
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 β-cells that included glucokinase (GK), and the pro-apoptotic protein, BADS. Mitochondria isolated from β-cells derived from β-cell specific insulin receptor knockout (βIRKO) mice exhibited reduced BADS, 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 βIRKOs could be explained, in part, by reduced expression and altered phosphorylation of BADS. The elevated phosphorylation of p70S6K and JNK1 was likely due to compensatory increase in IGF-1 receptor expression. Re-expression of insulin receptors in βIRKO cells partially restored the stoichiometry of the complex and mitochondrial function. These data indicate that insulin signaling regulates mitochondrial function and have implications for β-cell dysfunction in type 2 diabetes.
Description
License
Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.