Endocrinology：白藜芦醇治疗糖尿病的分子机制

美国德克萨斯大学西南医学研究中心发现，将白藜芦醇(resveratrol)直接注射到老鼠的大脑中，可以降低老鼠的胰岛素水平。经研究表明，白藜芦醇能直接作用于大脑中的某些蛋白质，或许能对糖尿病起到一定的预防作用。

之前研究人员给患2型糖尿病(非胰岛素依赖性糖尿病)口服白藜芦醇，发现该物质有降血糖的效果，但研究人员一直不清楚究竟是机体的那些组织产生该效果。而这篇研究报告表明，白藜芦醇降血糖功能的发挥，大脑起重要的作用。该报告发表Endocrinology网络版上。

但研究人员强调，该结果并不意味着使用越多红葡萄产品对身体就越好，主要原因在于白藜芦醇无法有效的穿越血脑屏障(bloodbrainbarrier)，而且每天大量饮用红葡萄酒还会对肝脏产生有害影响。因此，研究人员希望开发出白藜芦醇类似物来治疗饮食不良引发的糖尿病。

之前研究人员发现白藜芦醇能激活大脑中一类名为sirtuins的蛋白质，sirtuins能限制机体摄入过多热量，给动物注射白藜芦醇后，糖尿病病情得以改善。

研究人员对一组老鼠大脑直接注射白藜芦醇，另一组注射生理盐水安慰剂。再给两组老鼠提供高脂肪饮食。研究发现，注射生理盐水组的老鼠在使用高脂肪饮食后，胰岛素水平显著升高，而这种胰岛素灵敏性会随着持续性高脂肪饮食而降低。

注射白藜芦醇组的老鼠在实验开始阶段胰岛素水平降低，而在观察期过一半之后，胰岛素水平逐渐恢复正常——即使持续给老鼠提供高脂肪的食物。而且研究人员发现白藜芦醇确实可以激活sirtuin蛋白。（生物谷Bioon.com）

生物谷推荐原始出处：

Endocrinology, doi:10.1210/en.2009-0528

Central Administration of ResveratrolImproves Diet-Induced Diabetes

Giorgio Ramadori, Laurent Gautron, TeppeiFujikawa, Claudia R. Vianna, Joel K. Elmquist, and Roberto Coppari*

Division of Hypothalamic Research, Department of InternalMedicine (G.R., L.G., T.F., C.R.V., J.K.E., R.C.) and Department ofPharmacology (J.K.E.), The University of Texas Southwestern MedicalCenter, Dallas, Texas 75390-9077

Resveratrol is a natural polyphenolic compound that activatesnicotinamide adenosine dinucleotide-dependent deacetylase SIRT1.Resveratrol has recently been shown to exert potent antidiabeticactions when orally delivered to animal models of type 2 diabetes.However, the tissue(s) mediating these beneficial effects isunknown. Because SIRT1 is expressed in central nervous system (CNS)neurons known to control glucose and insulin homeostasis, wehypothesized that resveratrol antidiabetic effects are mediated bythe brain. Here, we report that long-term intracerebroventricularinfusion of resveratrol normalizes hyperglycemia and greatlyimproves hyperinsulinemia in diet-induced obese and diabetic mice.It is noteworthy that these effects are independent of changes inbody weight, food intake, and circulating leptin levels. Inaddition, CNS resveratrol delivery improves hypothalamic nuclearfactor-B inflammatory signaling by reducing acetylated-RelA/p65 andtotal RelA/p65 protein contents, and inhibitor of nuclearfactor-B  and IB kinase  mRNA levels. Furthermore, thistreatment leads to reduced hepatic phosphoenolpyruvatecarboxykinase 1 mRNA and protein levels and amelioratespyruvate-induced hyperglycemia in this mouse model of type 2diabetes. Collectively, our results unveiled a previouslyunrecognized key role for the CNS in mediating the antidiabeticactions of resveratrol.