Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell

Wiederkehr, Andreas; Wollheim, Claes

doi:10.1016/j.ceca.2007.11.004

Scientific article

English

Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell

Contributors

Wiederkehr, Andreas; Wollheim, Claes

Published in

Cell calcium, vol. 44, no. 1, p. 64-76

Publication date

2008

Abstract

Mitochondria play an essential role in metabolism-secretion coupling in the pancreatic beta-cell. Dysfunction of the organelle leads to impaired glucose-stimulated insulin secretion, as exemplified by the rare disease mitochondrial diabetes, which is caused by mutations in the mitochondrial DNA. In the excitable beta-cell, mitochondria generate ATP and possibly other coupling factors that promote plasma membrane depolarization and calcium influx triggering insulin exocytosis. Cytosolic calcium signals are relayed into the mitochondria, where the ion potentiates oxidative metabolism. Hormones such as glucagon-like peptide 1 (GLP-1) or neurotransmitter secretagogues stimulate the beta-cell by activating different signal transduction pathways eventually also raising mitochondrial calcium. Likewise, pharmacological inhibition of the Na(+)/Ca(2+) exchanger of the inner mitochondrial membrane augments intra-organellar calcium and insulin secretion. Islets obtained after autopsy from type 2 diabetic patients have altered mitochondrial morphology impaired glucose oxidation and reduced ATP generation, explaining defective insulin secretion. We hypothesize that the improvement of glucose-stimulated insulin secretion by sulfonylurea compounds in type 2 diabetic patients is in part due to their capacity to raise mitochondrial calcium, which is beneficial for the generation of metabolic coupling factors.

Keywords

Animals
Calcium/metabolism
DNA, Mitochondrial/genetics/metabolism
Diabetes Mellitus, Type 2/drug therapy/etiology/metabolism/physiopathology
Glycolysis/physiology
Humans
Insulin/deficiency/secretion
Insulin Resistance/physiology
Insulin-Secreting Cells/cytology/metabolism
Mitochondria/genetics/metabolism
Oxidoreductases/metabolism
Pancreas/cytology/metabolism
Sulfonylurea Compounds/therapeutic use

UNIGE affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

Citation (ISO format)

WIEDERKEHR, Andreas, WOLLHEIM, Claes. Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell. In: Cell calcium, 2008, vol. 44, n° 1, p. 64–76. doi: 10.1016/j.ceca.2007.11.004

Article (Accepted version)

Identifiers

PID : unige:2107
DOI : 10.1016/j.ceca.2007.11.004
PMID : 18191448

Journal ISSN

0143-4160

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19/06/2009 11:42:00

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19/06/2009 11:42:00

Update

14/03/2023 15:09:07

Status update

14/03/2023 15:09:07

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29/10/2024 11:45:33

Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation