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CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.


ABSTRACT: Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet ? cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from ? cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing ? cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the KATP channel, but instead due to reduced operation of the Na+-K+ pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na+-K+ pump is an important ATP-dependent regulator of ? cell function.

SUBMITTER: Briant LJB 

PROVIDER: S-EPMC6581793 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.

Briant Linford J B LJB   Dodd Michael S MS   Chibalina Margarita V MV   Rorsman Nils J G NJG   Johnson Paul R V PRV   Carmeliet Peter P   Rorsman Patrik P   Knudsen Jakob G JG  

Cell reports 20180601 11


Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet α cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from α cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decrease  ...[more]

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