Foufelle F, Ferré P
Unité INSERM 465, Centre de Recherches Biomédicales des Cordeliers, Université Paris 6, 15, rue de l'Ecole de Médecine, 75270 Paris.
J Soc Biol. 2001;195(3):243-8.
A number of tissues such as the brain must be continuously provided with glucose to meet their energy demand. In contrast, carbohydrate absorption during meals is a discontinuous process. Thus, we must store glucose when its is provided, release it or spare it when it is less abundant. Insulin, secreted by the pancreatic beta-cell is a key hormone in the adaptations of metabolic pathways linked to glucose homeostasis. It inhibits hepatic glucose production, promotes glucose storage in the liver and glucose uptake and storage in muscles and adipose tissues. This is achieved through the modifications of the activity of existing proteins (enzymes, transporters) but also through the regulation of gene expression. In the liver, when the diet is rich in carbohydrates, insulin is secreted and stimulates the expression of genes involved in glucose utilization (glucokinase, L-pyruvate kinase, lipogenic enzymes) and inhibits genes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes were poorly understood. Recently, the transcription factor Sterol Regulatory Element Binding Protein-1c (SREBP-1c) has been proposed as a key mediator of insulin transcriptional effects. Insulin increases the synthesis and nuclear abundance of this factor which when overexpressed in the liver mimics the effects of insulin on insulin-sensitive genes. This suggests that SREBP-1c could be involved in pathologies such as type 2 diabetes, obesity and more generally in insulin resistance syndromes.
许多组织，如大脑，必须持续获得葡萄糖以满足其能量需求。相比之下，进食期间碳水化合物的吸收是一个不连续的过程。因此，我们必须在葡萄糖供应充足时储存它，在供应不足时释放或节省它。胰腺β细胞分泌的胰岛素是与葡萄糖稳态相关的代谢途径适应性变化中的关键激素。它抑制肝脏葡萄糖生成，促进肝脏中葡萄糖的储存以及肌肉和脂肪组织对葡萄糖的摄取和储存。这是通过改变现有蛋白质（酶、转运蛋白）的活性以及调控基因表达来实现的。在肝脏中，当饮食富含碳水化合物时，胰岛素分泌并刺激参与葡萄糖利用的基因（葡萄糖激酶、L-丙酮酸激酶、脂肪生成酶）的表达，同时抑制参与葡萄糖生成的基因（磷酸烯醇式丙酮酸羧激酶）。胰岛素控制这些基因表达的机制此前了解甚少。最近，转录因子固醇调节元件结合蛋白-1c（SREBP-1c）被认为是胰岛素转录作用的关键介质。胰岛素增加该因子的合成及其在细胞核中的丰度，当在肝脏中过度表达时，它模拟胰岛素对胰岛素敏感基因的作用。这表明SREBP-1c可能与2型糖尿病、肥胖症以及更普遍的胰岛素抵抗综合征等病理状况有关。
