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Mitochondria and diabetes mellitus: untangling a conflictive relationship?

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Journal of Inherited Metabolic Disease

Summary

Diabetes mellitus is occasionally observed in patients with skeletal muscle respiratory chain deficiency, suggesting that skeletal muscle mitochondrial dysfunction might play a pathogenic role in type 2 diabetes (T2D). In support of this hypothesis, decreased muscle mitochondrial activity has been reported in T2D patients and in mouse models of diabetes. However, recent work by several groups suggests that decreased muscle mitochondrial function may be a consequence rather than a cause of diabetes, since decreased mitochondrial function in mice affords protection from diabetes and obesity. We review the data on this controversial but important issue of potential links between mitochondrial dysfunction and diabetes.

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Abbreviations

AIF:

apoptosis-inducing factor

HNF-1α:

hepatocyte nuclear factor-1α

IMCL:

intramyocellular lipid

MELAS:

mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

MIDD:

maternally inherited diabetes and deafness syndrome

MODY:

maturity-onset diabetes of the young

PGC-1α:

peroxisome proliferator-activated receptor γ co-activator 1α

PPAR:

peroxisome proliferator-activated receptor

T2D:

type 2 diabetes

TRMA:

thiamine-responsive megaloblastic anaemia

UCP2:

uncoupling protein 2

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Acknowledgement

This work was supported by grants from the AFM (Association Française contre les Myopathies), AMMi (Association contre les Maladies Mitochondriales), AFAF (Association française de l’ataxie de Friedreich), and Leducq foundation.

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Authors and Affiliations

  1. Hôpital Robert Debré, Paris, France

    M. Schiff, S. Loublier, A. Coulibaly, P. Bénit & P. Rustin

  2. Université Paris 7, Faculté de médecine Denis Diderot, IFR02, Paris, France

    M. Schiff, S. Loublier, A. Coulibaly, P. Bénit & P. Rustin

  3. Centre de référence Maladies Métaboliques, Hôpital Robert Debré, APHP, Paris, France

    M. Schiff & H. Ogier de Baulny

  4. INSERM U676, Bâtiment Ecran, Hôpital Robert Debré, 48, boulevard Sérurier, 75019, Paris, France

    P. Rustin

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  1. M. Schiff
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  2. S. Loublier
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Correspondence to P. Rustin.

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Communicating editor: Garry Brown

Competing interests: None declared

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Schiff, M., Loublier, S., Coulibaly, A. et al. Mitochondria and diabetes mellitus: untangling a conflictive relationship?. J Inherit Metab Dis 32, 684–698 (2009). https://doi.org/10.1007/s10545-009-1263-0

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