Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.
Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.
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DOI：
10.1371/journal.pone.0075111
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Casas F
中科院分区：
文献类型：
--
作者：
Bertrand C;Blanchet E;Pessemesse L;Annicotte JS;Feillet-Coudray C;Chabi B;Levin J;Fajas L;Cabello G;Wrutniak-Cabello C;Casas F
甲状腺骑术（TH）在能量支出调节中起着重要的调节作用，是线粒体活性的关键调节剂。在体内，我们在刺激线粒体生物发生时，我们在2个月大时产生了携带特定P43的小鼠。报道说，小鼠的p43耗竭在体内和孤立的胰岛胰岛素中诱导了胰岛素分泌的主要缺陷，以及葡萄糖刺激的胰岛素损失的损失。胰岛素水平以及葡萄糖耐受性或胰岛素敏感性，我们报告说，从4个月大的小鼠开始，缺乏P43的小鼠比野生型小鼠。与野生型相比，我们发现的寿命也适中降低。然而，如果长达12个月的葡萄糖耐受性，葡萄糖的年龄不变，葡萄糖刺激的年龄保持不变。 p43 - / - 小鼠的葡萄糖越来越不耐受。总结一下，我们证明了在小鼠中衰老的衰老中T3受体P43逐渐诱导了葡萄糖intlerance和胰岛素抵抗2型糖尿病的几种特征。
Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43−/− mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43−/− mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43−/− mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.
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影响因子：
4.8
作者：
Furuya, Fumihiko;Shimura, Hiroki;Kobayashi, Tetsuro
通讯作者：
Kobayashi, Tetsuro
影响因子：
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作者：
Kondo, Takuma;El Khattabi, Ilham;Sharma, Arun
通讯作者：
Sharma, Arun
影响因子：
4.8
作者：
Rochard, P;Rodier, A;Cabello, G
通讯作者：
Cabello, G
影响因子：
4.8
作者：
Pessemesse, Laurence;Schlernitzauer, Audrey;Casas, Francois
通讯作者：
Casas, Francois
影响因子：
3.7
作者：
Casas F;Pessemesse L;Grandemange S;Seyer P;Baris O;Gueguen N;Ramonatxo C;Perrin F;Fouret G;Lepourry L;Cabello G;Wrutniak-Cabello C
通讯作者：
Wrutniak-Cabello C