Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells

• DOI: 10.2337/db23-0056
• Publication Date: 2023-07-26T20:36:42Z
• Authors: Sarah L. Armour; Alexander Frueh; Margarita V. Chib...; Haiqiang Dou; Lidia Argemi-Munt...; Alexander Hamilton; Georgios Katzilie...; Peter Carmeliet; Benjamin Davies; Thomas Moritz; Lena Eliasson; Patrik Rorsman; Jakob G. Knudsen
• Keywords: Carbohydrate Metabolism; Alpha cell

Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When low, released α-cells to stimulate hepatic production. However, the mechanisms that regulate remain unclear. Here we show in α-cells, interaction between fatty acid oxidation metabolism controls secretion. The glucose-dependent inhibition relies on pyruvate dehydrogenase carnitine palmitoyl transferase 1a activity lowering mitochondrial by increases glucose. This results reduced intracellular ATP leads membrane repolarization These findings provide a new framework for metabolic regulation α-cell, where accounts stimulation Article Highlights It has become clear dysregulation α-cell function plays an important role development diabetes, but do not know how regulated. asked whether inhibits We found required inhibitory effects reductions ATP.