The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Lipoapoptosis in Beta-cells of Obese Prediabeticfa/fa Rats
Open accessAbstract
We reported that the lipoapoptosis of beta-cells observed in fat-laden islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an initiator of the apoptotic cascade and is induced by long-chain fatty acids (FA). Whereas the ceramide of cytokine-induced apoptosis may be derived from sphingomyelin hydrolysis, FA-induced ceramide overproduction seems to be derived from FA. We therefore semiquantified mRNA of serine palmitoyltransferase (SPT), which catalyzes the first step in ceramide synthesis. It was 2-3-fold higher in fa/fa islets than in +/+ controls. [3H]Ceramide formation from [3H]serine was 2.2-4. 5-fold higher in fa/fa islets. Triacsin-C, which blocks palmitoyl-CoA synthesis, and L-cycloserine, which blocks SPT activity, completely blocked [3H]ceramide formation from [3H]serine. Islets of fa/fa rats are unresponsive to the lipopenic action of leptin, which normally depletes fat and prevents FA up-regulation of SPT. To determine the role of leptin unresponsiveness in the SPT overexpression, we transferred wild type OB-Rb cDNA to their islets; now leptin completely blocked the exaggerated FA-induced increase of SPT mRNA while reducing the fat content. Beta-cell lipoapoptosis was partially prevented in vivo by treating prediabetic ZDF rats with L-cycloserine for 2 weeks. Ceramide content and DNA fragmentation both declined 40-50%. We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from FA and that blockade by SPT inhibitors prevents lipoapoptosis.
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Cites
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Self-citationLeptin receptor missense mutation in the fatty Zucker rat
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Direct antidiabetic effect of leptin through triglyceride depletion of tissues
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Self-citationAn update of the enzymology and regulation of sphingomyelin metabolism
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Self-citationRole of nitric oxide in obesity-induced beta cell disease.
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Cited by
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,225
Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
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Triglyceride accumulation protects against fatty acid-induced lipotoxicity
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Glucolipotoxicity: fuel excess and β-cell dysfunction
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Metadata
- Authors
- Shimabukuro, M., Higa, M., Zhou, Y.-T., Wang, M.-Y., Newgard, C. B., & Unger, R. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 273
- Issue
- 49
- Pages
- 32487-32490
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2001252698
- Cited by
- 395
- References
- 23
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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