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

• Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet a cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from a 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 alpha cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the K-ATP 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 alpha cell function.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

Nyckelord

sensitive k+ channels

human skeletal-muscle

alpha-cells

beta-cells

glucose-production

diabetes-mellitus

energy-metabolism

gene-expression

atp channels

delta-cells

Cell Biology

baulny ho

1995

journal of pediatrics

v127

p723

rich je

1973

science

v182

p171

Publikations- och innehållstyp

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