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Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.

Publication ,  Journal Article
Shimabukuro, M; Wang, MY; Zhou, YT; Newgard, CB; Unger, RH
Published in: Proc Natl Acad Sci U S A
August 4, 1998

Obesity causes its complications through functional and morphologic damage to remotely situated tissues via undetermined mechanisms. In one rodent model of obesity, the Zucker diabetic fatty fa/fa rat, overaccumulation of triglycerides in the pancreatic islets may be responsible for a gradual depletion of beta cells, leading to the most common complication of obesity, non-insulin-dependent diabetes mellitus. At the onset of non-insulin-dependent diabetes mellitus, the islets from fa/fa rats contain up to 100 times the fat content of islets from normal lean rats. Ultimately, about 75% of the beta cells disappear from these fat-laden islets as a consequence of apoptosis induced by long-chain fatty acids (FA). Here we quantify Bcl-2, the anti-apoptosis factor in these islets, and find that Bcl-2 mRNA and protein are, respectively, 85% and 70% below controls. In normal islets cultured in 1 mM FA, Bcl-2 mRNA declined by 68% and completely disappeared in fa/fa islets cultured in FA. In both groups, suppression was completely blocked by the fatty acyl-CoA synthetase inhibitor, triacsin C, evidence of its mediation by fatty acyl-CoA. To determine whether leptin action blocked FA-induced apoptosis, we cultured normal and fa/fa islets in 1 mM FA with or without leptin. Leptin completely blocked FA-induced Bcl-2 suppression in normal islets but had no effect on islets from fa/fa rats, which are unresponsive to leptin because of a mutation in their leptin receptors (OB-R). However, when wild-type OB-R is overexpressed in fa/fa islets, leptin completely prevented FA-induced Bcl-2 suppression and DNA fragmentation.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 4, 1998

Volume

95

Issue

16

Start / End Page

9558 / 9561

Location

United States

Related Subject Headings

  • Receptors, Leptin
  • Receptors, Cell Surface
  • Rats, Zucker
  • Rats
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Male
  • Leptin
  • Islets of Langerhans
  • Gene Expression Regulation
 

Citation

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Shimabukuro, M., Wang, M. Y., Zhou, Y. T., Newgard, C. B., & Unger, R. H. (1998). Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci U S A, 95(16), 9558–9561. https://doi.org/10.1073/pnas.95.16.9558
Shimabukuro, M., M. Y. Wang, Y. T. Zhou, C. B. Newgard, and R. H. Unger. “Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.Proc Natl Acad Sci U S A 95, no. 16 (August 4, 1998): 9558–61. https://doi.org/10.1073/pnas.95.16.9558.
Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH. Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9558–61.
Shimabukuro, M., et al. “Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.Proc Natl Acad Sci U S A, vol. 95, no. 16, Aug. 1998, pp. 9558–61. Pubmed, doi:10.1073/pnas.95.16.9558.
Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH. Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9558–9561.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 4, 1998

Volume

95

Issue

16

Start / End Page

9558 / 9561

Location

United States

Related Subject Headings

  • Receptors, Leptin
  • Receptors, Cell Surface
  • Rats, Zucker
  • Rats
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Male
  • Leptin
  • Islets of Langerhans
  • Gene Expression Regulation