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
Institution
Title
Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis.
Journal
Faseb Journal
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