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

Armour, Sarah L. ; Frueh, Alexander ; Chibalina, Margarita V. ; Dou, Haiqiang ; Argemi-Muntadas, Lidia ; Hamilton, Alexander LU ; Katzilieris-Petras, Georgios ; Carmeliet, Peter ; Davies, Benjamin and Moritz, Thomas , et al. (2023) In Diabetes 72(10). p.1446-1459
Abstract

Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from a-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic a-cells remain unclear. Here we show that in a-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehy-drogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of... (More)

Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from a-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic a-cells remain unclear. Here we show that in a-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehy-drogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the a-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
72
issue
10
pages
14 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:37494670
  • scopus:85171901684
ISSN
0012-1797
DOI
10.2337/db23-0056
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 by the American Diabetes Association.
id
e09708c5-7d04-49ac-bb64-85b5b3b93f30
date added to LUP
2023-12-04 16:49:36
date last changed
2024-04-17 13:10:24
@article{e09708c5-7d04-49ac-bb64-85b5b3b93f30,
  abstract     = {{<p>Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from a-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic a-cells remain unclear. Here we show that in a-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehy-drogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the a-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion.</p>}},
  author       = {{Armour, Sarah L. and Frueh, Alexander and Chibalina, Margarita V. and Dou, Haiqiang and Argemi-Muntadas, Lidia and Hamilton, Alexander and Katzilieris-Petras, Georgios and Carmeliet, Peter and Davies, Benjamin and Moritz, Thomas and Eliasson, Lena and Rorsman, Patrik and Knudsen, Jakob G.}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1446--1459}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic a-Cells}},
  url          = {{http://dx.doi.org/10.2337/db23-0056}},
  doi          = {{10.2337/db23-0056}},
  volume       = {{72}},
  year         = {{2023}},
}