PNAS：糖尿病治疗新药靶

近日，辛辛那提大学（UC）完成的一项新研究，载脂蛋白A-IV或许可以作为一个新的糖尿病治疗的潜在目标。

加州大学病理及实验室医学系教授Patrick Tso博士等研究人员发现载脂蛋白A-IV能降低血糖水平，并提升胰岛素分泌。

相关研究结果发表在2012年5月21日的PNAS杂志上。在网上的国家科学院的早期版本。

载脂蛋白A-IV由小肠为吸收脂肪而分泌的。以往的研究表明在胃绕道手术后，载脂蛋白A-IV水平会升高。

Tso研究小组发现缺乏载脂蛋白A-IV的小鼠糖耐量受损。这些老鼠在连续喂食高脂肪饮食时还会发展患有糖尿病。当注射载脂蛋白A-IV后，尽管给予高脂肪饮食，但小鼠胰岛素反应得到良好改善。

Tso研究团队也测试在糖尿病小鼠上注射载脂蛋白A-IV的影响，发现载脂蛋白A-IV会降低老鼠的血糖水平。

Tso说，他们的研究表明载脂蛋白A-IV类似一个肠促胰岛素，会造成进食后血糖升高的下降，增加胰岛素的释放。

Tso说：载脂蛋白A-IV有很长的半衰期（七至八个小时）。美国辛辛那提大学的研究成果已授权转让给马萨诸塞州Apofore公司，Apofore公司将进一步研究开发一种新型的靶向载脂蛋白A-IV的糖尿病治疗药物。（生物谷：Bioon.com）

doi:10.1073/pnas.1201433109
PMC:
PMID:

Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

Fei Wanga, Alison B. Kohana, Tammy L. Kindela, Kathryn L. Corbinb, Craig S. Nunemakerb, Silvana Obicic, Stephen C. Woodsd, W. Sean Davidsona, and Patrick Tsoa,1

Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca2+ influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV-/- mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV-/- mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.