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Article Dans Une Revue FASEB Journal Année : 2012

Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis

E. Blanchet
  • Fonction : Auteur
  • PersonId : 861709
Christelle Bertrand
J. S. Annicotte
  • Fonction : Auteur
A. Schlernitzauer
  • Fonction : Auteur
L. Pessemesse
  • Fonction : Auteur
  • PersonId : 1079744
Jonathan Levin
G. Fouret
  • Fonction : Auteur
C. Feillet-Coudray
B. Bonafos
  • Fonction : Auteur
  • PersonId : 1207246
G. Cabello
  • Fonction : Auteur
Chantal Wrutniak Cabello
François Casas

Résumé

Thyroid hormone is a major determinant of energy expenditure and a key regulator of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) that acts as a mitochondrial transcription factor of the organelle genome, which leads, in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Here we generated mice specifically lacking p43 to address its physiological influence. We found that p43 is required for normal glucose homeostasis. The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion. Moreover, a high-fat/high-sucrose diet elicited more severe glucose intolerance than that recorded in normal animals. In addition, we observed in p43(-/-) mice both a decrease in pancreatic islet density and in the activity of complexes of the respiratory chain in isolated pancreatic islets. These dysfunctions were associated with a down-regulation of the expression of the glucose transporter Glut2 and of Kir6.2, a key component of the K(ATP) channel. Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic beta-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor.
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Dates et versions

hal-02193048 , version 1 (24-07-2019)

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Citer

E. Blanchet, Christelle Bertrand, J. S. Annicotte, A. Schlernitzauer, L. Pessemesse, et al.. Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis. FASEB Journal, 2012, 26 (1), pp.40--50. ⟨10.1096/fj.11-186841⟩. ⟨hal-02193048⟩
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