Dataset Information

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Type B Pancreatic Cell, Pancreas

DISEASE(S): Diabetes Mellitus

SUBMITTER: Roman Fischer

LAB HEAD: Roman Fischer

PROVIDER: PXD012979 | Pride | 2019-04-10

REPOSITORIES: Pride

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Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.

Haythorne Elizabeth E Rohm Maria M van de Bunt Martijn M Brereton Melissa F MF Tarasov Andrei I AI Blacker Thomas S TS Sachse Gregor G Silva Dos Santos Mariana M Terron Exposito Raul R Davis Simon S Baba Otto O Fischer Roman R Duchen Michael R MR Rorsman Patrik P MacRae James I JI Ashcroft Frances M FM

Nature communications 20190606 1

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 glycolysi ...[more]

PMID: 31171772

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