How obesity causes diabetes in Zucker diabetic fatty rats.
The mechanisms of adipogenic diabetes in Zucker diabetic fatty (ZDF) rats, a model of obesity complicated by diabetes, are reviewed. In ZDF rats, a mutation in the leptin receptor, OB-R, is associated with leptin resistance, obesity, and increased fat content of islets. Exaggerated nitric oxide (NO) generation, attributed to high intracellular levels of long-chain fatty acids, impairs beta-cell function and prevents their compensation for obesity-induced diabetes. The resulting diabetic hyperglycemia can be completely prevented by agents that inhibit NO production.
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Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75235-8854, USA.