This study investigated the effects of cyclosporin (Cs) on insulin secretion and synthesis from the endocrine pancreas. With in vitro perfused pancreases from control and Cs-treated rats (1, 5,10, or 25 mg · kg−1 · day−1 for 2 wk), a dose-response relationship between Cs dose and inhibition of insulin secretion was demonstrated. Examination of the dynamic secretory response to a glucose stimulus (200 mg/dl) over a 3-h perfusion revealed an inhibition of all three secretory phases. Similarly, the ability of the pancreases to synthesize insulin decreased as a function of Cs dose. Reversibility of Cs toxicity on the pancreas was established by 2 wk after cessation of treatment. To evaluate the effect of Cs treatment in vivo, intravenous glucose tolerance tests were performed. Rats treated with 25 mg · kg−1 · day−1 Cs for 2 wk had significantly lower k values (slope of log glucose concentration over time) than controls. At 10 mg · kg−1 · day1, although curves that appeared abnormal were observed, k values were not significantly different from those of controls. In summary, this study demonstrates the profound inhibitory effect of Cs on the endocrine pancreas.
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Original Articles| April 01 1989
Synthesis-Secretion Coupling of Insulin: Effect of Cyclosporin
Susan L Gillison;
Stephen T Bartlett;
Address correspondence and reprint requests to Dr. Donald L. Curry, Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.
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Susan L Gillison, Stephen T Bartlett, Donald L Curry; Synthesis-Secretion Coupling of Insulin: Effect of Cyclosporin. Diabetes 1 April 1989; 38 (4): 465–470. https://doi.org/10.2337/diab.38.4.465
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