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

Publication ,  Journal Article
Wang, MY; Koyama, K; Shimabukuro, M; Newgard, CB; Unger, RH
Published in: Proc Natl Acad Sci U S A
January 20, 1998
Published version (DOI) Link to item

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

Duke Scholars

Christopher Bang Newgard
Author Christopher Bang Newgard Pharmacology & Cancer Biology

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.95.2.714

ISSN

0027-8424

Publication Date

January 20, 1998

Volume

95

Issue

2

Start / End Page

714 / 718

Location

United States

Related Subject Headings

  • Receptors, Leptin
  • Receptors, Cell Surface
  • Rats, Zucker
  • Rats
  • Proteins
  • Obesity
  • Mutation
  • Leptin
  • Islets of Langerhans
  • Gene Transfer Techniques
 

Citation

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MLA
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Wang, M. Y., Koyama, K., Shimabukuro, M., Newgard, C. B., & Unger, R. H. (1998). OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. Proc Natl Acad Sci U S A, 95(2), 714–718. https://doi.org/10.1073/pnas.95.2.714
Wang, M. Y., K. Koyama, M. Shimabukuro, C. B. Newgard, and R. H. Unger. “OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype.” Proc Natl Acad Sci U S A 95, no. 2 (January 20, 1998): 714–18. https://doi.org/10.1073/pnas.95.2.714.
Wang MY, Koyama K, Shimabukuro M, Newgard CB, Unger RH. OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):714–8.
Wang, M. Y., et al. “OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype.” Proc Natl Acad Sci U S A, vol. 95, no. 2, Jan. 1998, pp. 714–18. Pubmed, doi:10.1073/pnas.95.2.714.
Wang MY, Koyama K, Shimabukuro M, Newgard CB, Unger RH. OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):714–718.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.95.2.714

ISSN

0027-8424

Publication Date

January 20, 1998

Volume

95

Issue

2

Start / End Page

714 / 718

Location

United States

Related Subject Headings

  • Receptors, Leptin
  • Receptors, Cell Surface
  • Rats, Zucker
  • Rats
  • Proteins
  • Obesity
  • Mutation
  • Leptin
  • Islets of Langerhans
  • Gene Transfer Techniques