Characterization of the role of orexin in controlling glucose and lipid metabolism - identification of potential novel therapeutic application in diabetes mellitus type 2

食欲素在控制葡萄糖和脂质代谢中的作用的表征 - 鉴定 2 型糖尿病的潜在新治疗应用

• 批准号: 71227275
• 负责人: Professor Dr. Mathias Strowski
• 金额: --
• 依托单位: Medizinische Klinik mit SP Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen (CVK)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/71227275?language=en
• 关键词: Characterization; role; orexin; controlling; glucose

Orexin modulates food intake. Decreased concentration of orexin in serum and cerebrospinal fluid is a hallmark of narcolepsy, Narcolepsia is associated with impaired glucose tolerance. Own preliminary data suggest that orexin stimulates insulin and decreases glucagon secretion, and proglucagon gene transcription through a novel mechanism. In adipocytes, orexin can stimulate the production of leptin, which is known to enhance insulin sensitivity and energy expenditure. Aim of the project is to characterize the role of orexin in regulating glucose homeostasis and to delineate the underlying mechanisms. In vivo, we plan to study the role of orexin in controlling glucose and lipid metabolism in normoglycemic and type 2 diabetic animal models. Molecular mechanisms of orexin action will be evaluated at the cellular level using isolated rodent and human pancreatic islets, primary cell preparations, and permanent models of pancreatic A- and B-cells, and adipocytes. In humans, the association between plasma orexin and blood glucose concentrations in healthy and obese individuals as well as in patients with type 2 diabetes mellitus will be studied. Furthermore, the role of orexin in regulating the secretory activity of human pancreatic islets will be delineated. The results of the study may have clinical implications to decipher the impact of orexin in controlling glucose metabolism and its contribution to the pathophysiology and possible therapy of type 2 diabetes mellitus.

食欲素调节食物摄入量。血清和脑脊液中食欲素浓度降低是发作性睡病的一个特征，发作性睡病与糖耐量受损有关。自己的初步数据表明，食欲素通过一种新的机制刺激胰岛素和减少胰高血糖素的分泌，并通过一种新的机制转录原胰高血糖素。在脂肪细胞中，食欲素可以刺激瘦素的产生，瘦素已知可以增强胰岛素敏感性和能量消耗。该项目的目的是表征增食欲素在调节血糖稳态中的作用，并描述其潜在的机制。在体内，我们计划研究增食欲素在正常血糖和2型糖尿病动物模型中控制糖脂代谢的作用。食欲素作用的分子机制将使用分离的啮齿动物和人胰岛、原代细胞制备和胰腺A细胞和B细胞以及脂肪细胞的永久模型在细胞水平上进行评估。在人类中，将研究健康人、肥胖者以及2型糖尿病患者的血浆增食欲素和血糖浓度之间的关系。此外，还将阐明增食欲素在调节人胰岛分泌活动中的作用。这项研究的结果可能对破译增食欲素在控制糖代谢中的影响以及它在2型糖尿病的病理生理和可能的治疗中的贡献具有临床意义。