OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype
AUTOR(ES)
Wang, May-Yun
FONTE
The National Academy of Sciences
RESUMO
In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islets have an ≈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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18486Documentos Relacionados
- Expressão do gene da leptina e seu receptor Ob-Rb no parênquima mamário de novilhas leiteiras
- Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice
- Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity
- Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets of ob/ob mice.
- Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.