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首页> 外文期刊>Frontiers in neuroendocrinology >Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities.
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Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities.

机译:胰岛素和瘦蛋白:具有重叠的生理和细胞内信号传导能力的肥胖信号。

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摘要

The adipocyte-derived hormone leptin and the pancreatic beta cell-derived hormone insulin each function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity. Although these two hormones, and the receptors on which they act, are unrelated and structurally distinct, they exert overlapping effects in the arcuate nucleus, a key hypothalamic area involved in energy homeostasis. Defects in either insulin or leptin signaling in the brain result in hyperphagia, disordered glucose homeostasis, and reproductive dysfunction. To explain this striking physiological overlap, we hypothesize that hypothalamic insulin and leptin signaling converge upon a single intracellular signal transduction pathway, known as the insulin-receptor-substrate phosphatidylinositol 3-kinase pathway. Here we synthesize data from a variety of model systems in which such "cross-talk" between insulin and leptin signal transduction has either been observed or can be inferred, discuss our own datademonstrating that insulin and leptin both activate hypothalamic phosphatidylinositol 3-kinase signaling, and discuss the significance of such convergence with respect to neuronal function in normal individuals and in pathological states such as obesity. Identification of the key early molecular events mediating the action of both insulin and leptin in hypothalamic neurons promises new insight into the regulation of these neurons in health and disease.
机译:脂肪细胞源性激素瘦素和胰腺β细胞源性激素胰岛素在调节体内肥胖的内分泌反馈回路中均作为下丘脑的传入信号。尽管这两种激素及其作用的受体无关且在结构上不同,但它们在弓形核(能量稳态的关键下丘脑区域)中发挥重叠作用。脑中胰岛素或瘦素信号传导的缺陷会导致食欲亢进,葡萄糖稳态失调和生殖功能障碍。为了解释这种惊人的生理重叠,我们假设下丘脑胰岛素和瘦素信号转导在单个细胞内信号转导途径上,即胰岛素受体-底物磷脂酰肌醇3-激酶途径。在这里,我们综合了各种模型系统的数据,其中已经观察到或可以推断出胰岛素和瘦素信号转导之间的这种“串扰”,讨论我们自己的数据,证明胰岛素和瘦素均激活下丘脑磷脂酰肌醇3激酶信号传导,并讨论了这种收敛对正常人和病理状态(例如肥胖)中神经元功能的重要性。识别介导下丘脑神经元中胰岛素和瘦素的作用的关键早期分子事件,有望为健康和疾病中这些神经元的调节提供新的见解。

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