文章基本信息

标题：OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype
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作者：May-Yun Wang ; Kazunori Koyama ; Michio Shimabukuro 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：2
页码：714-718
DOI：10.1073/pnas.95.2.714
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islets have an {approx}50-fold increase in fat (TG), overproduce nitric oxide (NO), and lack a normal proinsulin mRNA response to fatty acids. We overexpressed the wild-type full-length "b" isoform of the leptin receptor (OB-Rb) in ZDF islets by perfusing ZDF pancreata with recombinant adenovirus containing the cDNA encoding OB-Rb. In cultured islets isolated from these animals, leptin lowered islet TG by 87% and completely blocked TG formation from free fatty acids. Overproduction of NO was reduced, and the preproinsulin mRNA response to free fatty acids was restored. This establishes defective leptin action as the proximate cause of lipotoxic diabetes in ZDF rats.