Abstract：
: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 decreases glucagon output by depolarizing α 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 α cell function.
journal_name
Cell Repjournal_title
Cell reportsauthors
Briant LJB,Dodd MS,Chibalina MV,Rorsman NJG,Johnson PRV,Carmeliet P,Rorsman P,Knudsen JGdoi
10.1016/j.celrep.2018.05.035subject
Has Abstractpub_date
2018-06-12 00:00:00pages
3300-3311issue
11issn
2211-1247pii
S2211-1247(18)30781-2journal_volume
23pub_type
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