Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells
Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.
Item Type | Article |
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Subjects |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
Date Deposited | 26 Jul 2024 12:36 |
Last Modified | 26 Jul 2024 12:36 |
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Read more research from the creator(s):
- Haythorne, Elizabeth
- Rohm, Maria
- van de Bunt, Martijn
- Brereton, Melissa F
- Tarasov, Andrei I
- Blacker, Thomas S
- Sachse, Gregor
- Silva Dos Santos, Mariana
- Terron Exposito, Raul
- Davis, Simon
- Baba, Otto
- Fischer, Roman
- Duchen, Michael R
- Rorsman, Patrik
- MacRae, James I
- Ashcroft, Frances M
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