Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis.

Details

Serval ID
serval:BIB_C8B0CC971FB3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis.
Journal
Faseb Journal
Author(s)
Blanchet E., Bertrand C., Annicotte J.S., Schlernitzauer A., Pessemesse L., Levin J., Fouret G., Feillet-Coudray C., Bonafos B., Fajas L., Cabello G., Wrutniak-Cabello C., Casas F.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Publication state
Published
Issued date
2012
Volume
26
Number
1
Pages
40-50
Language
english
Abstract
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 β-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor.
Keywords
Animals, Blood Glucose/metabolism, Body Temperature/physiology, Cell Line, Dietary Fats/pharmacology, Dietary Sucrose/pharmacology, Glucose Intolerance/genetics, Glucose Intolerance/metabolism, Homeostasis/physiology, Humans, Hypothermia/genetics, Hypothermia/metabolism, Insulin/blood, Insulin/secretion, Insulin-Secreting Cells/cytology, Insulin-Secreting Cells/physiology, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mitochondria/metabolism, Myoblasts/cytology, Myoblasts/physiology, Receptors, Thyroid Hormone/genetics, Receptors, Thyroid Hormone/metabolism, Thyroid Hormones/blood
Pubmed
Web of science
Create date
07/03/2013 16:42
Last modification date
20/08/2019 16:43
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