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

May Yun Wang, Kazunori Koyama, Michio Shimabukuro, Christopher B. Newgard, Roger H. Uncer

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)714-718
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number2
DOIs
StatePublished - Jan 20 1998

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Retinoblastoma Genes
Leptin Receptors
Leptin
Nonesterified Fatty Acids
Nitric Oxide
Phenotype
Proinsulin
Messenger RNA
Islets of Langerhans
Adenoviridae
Pancreas
Protein Isoforms
Fatty Acids
Complementary DNA
Fats
preproinsulin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. / Wang, May Yun; Koyama, Kazunori; Shimabukuro, Michio; Newgard, Christopher B.; Uncer, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 2, 20.01.1998, p. 714-718.

Research output: Contribution to journalArticle

Wang, May Yun ; Koyama, Kazunori ; Shimabukuro, Michio ; Newgard, Christopher B. ; Uncer, Roger H. / OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 2. pp. 714-718.
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