title: Synthesis-secretion coupling of insulin. Effect of cyclosporin.
abstract: 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.day-1, 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.
authors.affiliation: Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis 95616.
authors.forename: S L
authors.initials: SL
authors.lastname: Gillison
authors.forename: S T
authors.initials: ST
authors.lastname: Bartlett
authors.forename: D L
authors.initials: DL
authors.lastname: Curry
mesh_terms: D000818:Animals; D003524:Cyclosporins / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
chemical_list: D003524:Cyclosporins; D007328:Insulin; D005947:Glucose