Departments of Physiology and Medicine, University of Toronto, Toronto, Canada.
Cell Cycle. 2010 Aug 15;9(16):3186-93. doi: 10.4161/cc.9.16.12552. Epub 2010 Aug 4.
Obesity and type 2 diabetes mellitus represent a significant global health crisis. These two interrelated diseases are typified by perturbed insulin signaling in the hypothalamus. Using novel hypothalamic cell lines, we have begun to elucidate the molecular and intracellular mechanisms involved in the hypothalamic control of energy homeostasis and insulin resistance. In this review, we present evidence of insulin and glucose signaling pathways that lead to changes in neuropeptide gene expression. We have identified some of the molecular mechanisms involved in the control of de novo hypothalamic insulin mRNA expression. And finally, we have defined key mechanisms involved in the etiology of cellular insulin resistance in hypothalamic neurons that may play a fundamental role in cases of high levels of insulin or saturated fatty acids, often linked to the exacerbation of obesity and diabetes.
肥胖和 2 型糖尿病代表了重大的全球健康危机。这两种相互关联的疾病以下丘脑胰岛素信号紊乱为特征。我们使用新型的下丘脑细胞系，开始阐明参与下丘脑控制能量平衡和胰岛素抵抗的分子和细胞内机制。在这篇综述中，我们提出了胰岛素和葡萄糖信号通路的证据，这些通路导致神经肽基因表达的变化。我们已经确定了一些参与新的下丘脑胰岛素 mRNA 表达控制的分子机制。最后，我们定义了涉及下丘脑神经元中细胞胰岛素抵抗病因的关键机制，这些机制可能在高水平胰岛素或饱和脂肪酸的情况下发挥重要作用，这些情况通常与肥胖和糖尿病的恶化有关。
