OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype

被引：94

作者：

Wang, MY

Koyama, K

Shimabukuro, M

Newgard, CB

Unger, RH

机构：

[1] Univ Texas, SW Med Ctr, Gifford Labs Diabet Res, Dallas, TX 75235 USA

[2] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA

[3] Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA

[4] Dept Vet Affairs Med Ctr, Dallas, TX 75216 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1998年 / 95卷 / 02期

关键词：

D O I：

10.1073/pnas.95.2.714

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islets have an approximate to 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.

引用

页码：714 / 718

页数：5

共 23 条

[1] The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors [J].