What question did this study set out to answer?

To determine the molecular mechanism linking fatty acids to ceramide synthesis and lipoapoptosis in beta-cells of obese prediabetic fa/fa rats, and assess whether blocking this pathway prevents cell death.

December 1, 1998Journal of Biological ChemistryOpen Access

Lipoapoptosis in Beta-cells of Obese Prediabeticfa/fa Rats

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Authors

MSMichio ShimabukuroPreventive Cardiology MHMoritake HigaTomishiro Central Hospital YZYan-Ting ZhouThe University of Texas Southwestern Medical Center

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Implication

Preclinical study reveals that blocking ceramide synthesis prevents beta-cell lipoapoptosis in obese prediabetic rats, suggesting therapeutic potential for preserving islet function.

Key Points

To determine the molecular mechanism linking fatty acids to ceramide synthesis and lipoapoptosis in beta-cells of obese prediabetic fa/fa rats, and assess whether blocking this pathway prevents cell death.
Measured serine palmitoyltransferase (SPT) mRNA and [3H]ceramide formation from [3H]serine in islets isolated from fa/fa Zucker Diabetic Fatty rats and +/+ controls, testing inhibitors Triacsin-C and L-cycloserine.
Transduced fa/fa islets with wild-type leptin receptor (OB-Rb) cDNA to assess whether restoring leptin responsiveness normalizes SPT expression and fat content.
Administered the SPT inhibitor L-cycloserine in vivo to prediabetic ZDF rats for 2 weeks to evaluate effects on islet ceramide levels and DNA fragmentation.
Islets from fa/fa rats exhibited 2- to 3-fold higher SPT mRNA and a 2.2- to 4.5-fold increase in ceramide formation compared to +/+ controls, both of which were completely blocked by Triacsin-C and L-cycloserine.
Gene delivery of wild-type OB-Rb restored leptin responsiveness, completely suppressing the fatty acid-induced elevation of SPT mRNA and decreasing islet fat.
In vivo treatment with L-cycloserine for 2 weeks reduced islet ceramide content and apoptotic DNA fragmentation by 40% to 50% in prediabetic ZDF rats.

Cite This Study

Shimabukuro et al. (1998) studied this question.

synapsesocial.com/papers/69d7d44311d83f35e5ae2caa https://doi.org/10.1074/jbc.273.49.32487

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Implication

Preclinical study reveals that blocking ceramide synthesis prevents beta-cell lipoapoptosis in obese prediabetic rats, suggesting therapeutic potential for preserving islet function.

Lipoapoptosis in Beta-cells of Obese Prediabeticfa/fa Rats

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Implication

Key Points

Cite This Study

Lipoapoptosis in Beta-cells of Obese Prediabeticfa/fa Rats

Discussion

Member takes

Implication

Key Points

Cite This Study

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