| First Author | Blanchet E | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 1 | Pages | 40-50 |
| PubMed ID | 21914860 | Mgi Jnum | J:179839 |
| Mgi Id | MGI:5304235 | Doi | 10.1096/fj.11-186841 |
| Citation | Blanchet E, et al. (2012) Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis. FASEB J 26(1):40-50 |
| abstractText | 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.-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. Mitochondrial T3 receptor p43 regulates insulin secretion and glucose homeostasis. |
