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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells. / Armour, Sarah L.; Frueh, Alexander; Chibalina, Margarita V.; Dou, Haiqiang; Argemi-Muntadas, Lidia; Hamilton, Alexander; Katzilieris-Petras, Georgios; Carmeliet, Peter; Davies, Benjamin; Moritz, Thomas; Eliasson, Lena; Rorsman, Patrik; Knudsen, Jakob G.

In: Diabetes, Vol. 72, No. 10, 2023, p. 1446-1459.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Armour, SL, Frueh, A, Chibalina, MV, Dou, H, Argemi-Muntadas, L, Hamilton, A, Katzilieris-Petras, G, Carmeliet, P, Davies, B, Moritz, T, Eliasson, L, Rorsman, P & Knudsen, JG 2023, 'Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells', Diabetes, vol. 72, no. 10, pp. 1446-1459. https://doi.org/10.2337/db23-0056

APA

Armour, S. L., Frueh, A., Chibalina, M. V., Dou, H., Argemi-Muntadas, L., Hamilton, A., Katzilieris-Petras, G., Carmeliet, P., Davies, B., Moritz, T., Eliasson, L., Rorsman, P., & Knudsen, J. G. (2023). Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells. Diabetes, 72(10), 1446-1459. https://doi.org/10.2337/db23-0056

Vancouver

Armour SL, Frueh A, Chibalina MV, Dou H, Argemi-Muntadas L, Hamilton A et al. Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells. Diabetes. 2023;72(10):1446-1459. https://doi.org/10.2337/db23-0056

Author

Armour, Sarah L. ; Frueh, Alexander ; Chibalina, Margarita V. ; Dou, Haiqiang ; Argemi-Muntadas, Lidia ; Hamilton, Alexander ; Katzilieris-Petras, Georgios ; Carmeliet, Peter ; Davies, Benjamin ; Moritz, Thomas ; Eliasson, Lena ; Rorsman, Patrik ; Knudsen, Jakob G. / Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells. In: Diabetes. 2023 ; Vol. 72, No. 10. pp. 1446-1459.

Bibtex

@article{58d028544d2e47b7b1d12e372f821863,
title = "Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells",
abstract = "Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from α-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic α-cells remain unclear. Here we show that in α-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase 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 α-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion. ARTICLE HIGHLIGHTS: It has become clear that dysregulation of glucagon secretion and α-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in α-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.",
author = "Armour, {Sarah L.} and Alexander Frueh and Chibalina, {Margarita V.} and Haiqiang Dou and Lidia Argemi-Muntadas and Alexander Hamilton and Georgios Katzilieris-Petras and Peter Carmeliet and Benjamin Davies and Thomas Moritz and Lena Eliasson and Patrik Rorsman and Knudsen, {Jakob G.}",
note = "Publisher Copyright: {\textcopyright} 2023 by the American Diabetes Association.",
year = "2023",
doi = "10.2337/db23-0056",
language = "English",
volume = "72",
pages = "1446--1459",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "10",

}

RIS

TY - JOUR

T1 - Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells

AU - Armour, Sarah L.

AU - Frueh, Alexander

AU - Chibalina, Margarita V.

AU - Dou, Haiqiang

AU - Argemi-Muntadas, Lidia

AU - Hamilton, Alexander

AU - Katzilieris-Petras, Georgios

AU - Carmeliet, Peter

AU - Davies, Benjamin

AU - Moritz, Thomas

AU - Eliasson, Lena

AU - Rorsman, Patrik

AU - Knudsen, Jakob G.

N1 - Publisher Copyright: © 2023 by the American Diabetes Association.

PY - 2023

Y1 - 2023

N2 - Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from α-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic α-cells remain unclear. Here we show that in α-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase 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 α-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion. ARTICLE HIGHLIGHTS: It has become clear that dysregulation of glucagon secretion and α-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in α-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.

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

U2 - 10.2337/db23-0056

DO - 10.2337/db23-0056

M3 - Journal article

C2 - 37494670

AN - SCOPUS:85171901684

VL - 72

SP - 1446

EP - 1459

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -

ID: 368723129