PMID: 15220200Jun 29, 2004Paper

Insulin feedback alters mitochondrial activity through an ATP-sensitive K+ channel-dependent pathway in mouse islets and beta-cells

Diabetes
Craig S NunemakerLeslie S Satin

Abstract

Recent work suggests that insulin may exert both positive and negative feedback directly on pancreatic beta-cells. To investigate the hypothesis that insulin modulates beta-cell metabolism, mouse islets and beta-cell clusters were loaded with rhodamine 123 to dynamically monitor mitochondrial membrane potential (DeltaPsi(m)). Spontaneous oscillations in DeltaPsi(m) (period: 218 +/- 26 s) were observed in 17 of 30 islets exposed to 11.1 mmol/l glucose. Acute insulin application (100 nmol/l) hyperpolarized DeltaPsi(m), indicating a change in mitochondrial activity. The ATP-sensitive K(+) (K(ATP)) channel opener diazoxide or the l-type calcium channel blocker nifedipine mimicked the effect of insulin, suggesting that insulin activates K(ATP) channels to hyperpolarize DeltaPsi(m) by inhibiting calcium influx. Treatment with forskolin, which increases endogenous insulin secretion, also mimicked the effect of exogenous insulin, suggesting physiological feedback. Pretreatment with nifedipine or the K(ATP) inhibitor glyburide prevented insulin action, further implicating a K(ATP) channel pathway. Together, these data suggest a feedback mechanism whereby insulin receptor activation opens K(ATP) channels to inhibit further secretion. The...Continue Reading

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Citations

Aug 17, 2011·Diabetes, Obesity & Metabolism·J N WalkerP Rorsman
May 26, 2010·Theoretical Biology & Medical Modelling·Leonid E Fridlyand, Louis H Philipson
Mar 10, 2010·Molecular and Cellular Endocrinology·William S CrimCraig S Nunemaker
Apr 29, 2005·Diabetes/metabolism Research and Reviews
Sep 7, 2004·Biophysical Journal·Richard BertramArthur Sherman
May 26, 2012·Islets·Kyungreem HanMooyoung Choi
Sep 8, 2005·American Journal of Physiology. Endocrinology and Metabolism·Emma HeartBarbara E Corkey
Dec 31, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·H KangD S Koh
Mar 5, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Xiaozhuo ChenAili Guo

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