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Glucose Controls Gl...
Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells
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- Armour, Sarah L. (author)
- University of Copenhagen
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- Frueh, Alexander (author)
- University of Copenhagen
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- Chibalina, Margarita V. (author)
- University of Oxford
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- Dou, Haiqiang, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Sahlgrenska Academy
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- Argemi-Muntadas, Lidia (author)
- Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Hamilton, Alexander (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,University of Copenhagen
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- Katzilieris-Petras, Georgios (author)
- University of Copenhagen
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- Carmeliet, Peter (author)
- Leuven Cancer Institute,Sun Yat-sen University,Aarhus University
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- Davies, Benjamin (author)
- Wellcome Trust Centre for Human Genetics
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- Moritz, Thomas (author)
- Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Rorsman, Patrik, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Oxford,Sahlgrenska Academy
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- Knudsen, Jakob G. (author)
- University of Copenhagen
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: DIABETES. - 0012-1797 .- 1939-327X. ; 72:10, s. 1446-1459
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Abstract
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- Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from alpha-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic alpha-cells remain unclear. Here we show that in alpha-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 alpha-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 alpha-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 alpha-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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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DIABETES
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- By the author/editor
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Armour, Sarah L.
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Frueh, Alexander
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Chibalina, Marga ...
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Dou, Haiqiang, 1 ...
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Argemi-Muntadas, ...
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Hamilton, Alexan ...
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Katzilieris-Petr ...
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Carmeliet, Peter
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Davies, Benjamin
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Moritz, Thomas
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Eliasson, Lena
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Rorsman, Patrik, ...
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Knudsen, Jakob G ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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DIABETES
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University of Gothenburg
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Lund University