Leptin effects on pancreatic beta-cell gene expression and function.
Leptin effects on pancreatic beta-cell gene expression and function.
复制标题
瘦素对胰腺β细胞基因表达和功能的影响。
作者：
J. Seufert
瘦素激素由白色脂肪细胞分泌，血清瘦素水平与脂肪组织质量相关。瘦素首次被描述为通过特定受体（瘦素受体[ObR]）作用于下丘脑的饱腹感中枢，以限制食物摄入并增强能量消耗。瘦素的重要外周作用包括抑制胰腺β细胞的胰岛素生物合成和分泌。反过来，胰岛素刺激脂肪组织分泌瘦素，建立激素调节反馈回路——所谓的“脂肪-岛轴”。胰岛β细胞中瘦素信号通路涉及多种信号转导途径。我们已经确定胰岛素原基因和蛋白磷酸酶1基因是瘦素抑制基因，细胞因子信号3蛋白抑制基因是瘦素诱导基因。瘦素的分子作用最终限制胰岛素分泌和生物合成，使葡萄糖稳态适应体脂量。然而，在大多数超重个体中，瘦素对体重的生理调节似乎受到干扰，这代表了“瘦素抵抗”。胰腺β细胞水平的瘦素抵抗可能导致脂肪-岛轴的失调，并促进超重患者高胰岛素血症和显性2型糖尿病的发展。
The hormone leptin is secreted from white adipocytes, and serum levels of leptin correlate with adipose tissue mass. Leptin was first described to act on the satiety center in the hypothalamus through specific receptors (leptin receptor [ObR]) to restrict food intake and enhance energy expenditure. Important peripheral actions of leptin involve inhibition of insulin biosynthesis and secretion in pancreatic beta-cells. In turn, insulin stimulates leptin secretion from adipose tissue, establishing a hormonal regulatory feedback loop-the so-called "adipo-insular axis." Multiple signal transduction pathways are involved in leptin signaling in pancreatic beta-cells. We have identified the proinsulin gene and protein phosphatase 1 gene as leptin repressed genes and the gene for the suppressor of cytokine signaling 3 protein as a leptin-induced gene in pancreatic beta-cells. The molecular effects of leptin culminate to restrict insulin secretion and biosynthesis to adapt glucose homeostasis to the amount of body fat. In most overweight individuals, however, physiological regulation of body weight by leptin seems to be disturbed, representing "leptin resistance." This leptin resistance at the level of the pancreatic beta-cell may contribute to dysregulation of the adipo-insular axis and promote the development of hyperinsulinemia and manifest type 2 diabetes in overweight patients.