Effect of Cyclosporin-A on Insulin Secretion in Vitro

Laube, F.; Hj, Hahn

doi:10.1055/s-2007-1013445

Cited by 14 publications

(8 citation statements)

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“…17 One study, using a short in vitro incubation with the drug, failed to show effects on insulin release. 18 This, taken with the present results, suggests that time of exposure is an important factor in the effect on insulin secretion. At doses in the therapeutic range, we could not identify morphologic changes in the pancreas at the light microscopic level, including the immunoperoxidase stain for insulin.…”

Section: Discussionsupporting

confidence: 86%

Effects of Cyclosporine on Glucose Tolerance in the Rat

Yale

Grose

et al. 1985

Diabetes

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In a study of prevention of spontaneous diabetes in BB rats by therapeutic doses of cyclosporine (10 mg/kg/day), the male control non-diabetes-prone rats showed glucose intolerance after a 0.25 g/kg glucose load by gavage, at 90 and 130 days of treatment. Non-BB male Wistar rats treated similarly showed glucose intolerance at 1 wk of treatment, with progressive worsening for 5 wk, then sustained up to 12 wk of treatment. Fasting euglycemia was maintained, but both pre- and postchallenge plasma insulin levels were significantly lower with cyclosporine at several time points. Total pancreatic insulin was decreased to one-third that of control after 5 wk. After withdrawal of cyclosporine, glucose tolerance returned to normal in 2 wk. Sprague-Dawley rats responded similarly and in both strains, an increase in the cyclosporine dose to 15 mg/kg/day augmented the glucose intolerance. These results demonstrate that therapeutic doses of this agent induce reversible glucose intolerance due, in part, to inhibition of insulin secretion and also possibly inhibition of synthesis, though a peripheral effect is not excluded. This hyperglycemic effect of cyclosporine has implications for its potential use in type I diabetes mellitus, transplantation, and other autoimmune disease.

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Section: Discussionsupporting

confidence: 86%

Effects of Cyclosporine on Glucose Tolerance in the Rat

Yale

Grose

et al. 1985

Diabetes

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“…These observations were supported by Helmchen et al (5), who reported severe degranulation in islet (B-cells from rats treated with the drug. On the other hand, Laube and Hahn (18) found no effects of cyclosporin on rat isolated islets. Robertson (7) found inhibition of glucose-induced insulin secretion from both rat isolated islets and a clonal (3-cell line.…”

Section: Discussionmentioning

confidence: 95%

Intravenous Glucose Tolerance and Pancreatic Islet β-Cell Function in Patients With Multiple Sclerosis During 2-yr Treatment With Cyclosporin

1989

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Cyclosporin is an immunosuppressive drug used with increasing frequency in patients with diabetes mellitus both as experimental primary therapy for insulin-dependent diabetes mellitus and as therapy accompanying pancreatic transplantation. However, reports have appeared contending that cyclosporin causes glucose intolerance and inhibits pancreatic islet beta-cell function. Consequently, concern has been raised that the beneficial effects of immunosuppression may be offset by adverse metabolic effects of the drug. To address this issue, we examined intravenous glucose tolerance and pancreatic islet beta-cell function in a group of nondiabetic multiple sclerosis patients before and during a 2-yr course of cyclosporin or placebo therapy. Patients were randomly assigned to one of the two drug groups and followed in a double-blind manner. Basal levels of glucose, insulin, and C-peptide as well as glucose disappearance rates and pancreatic islet beta-cell function after stimulation with intravenous glucose and arginine were determined immediately before therapy and after 3 wk, 6 mo, 1 yr, and 2 yr of therapy. No abnormalities in these parameters were observed in the cyclosporin of the placebo-treated group. It appears that cyclosporin can be give in conventional doses for as long as 2 yr without encountering evidence for impaired glucose homeostasis. However, whether adverse effects will materialize over longer periods of drug use remains a question.

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“…Immediately after intrahepatic injection, the islets are denervated and are vascularized by the portal vein blood. This is surely a very unfavorable condition, since (a) the autonomic modulation of insulin secretion is important in maintaining an insulin secretory rate properly tuned to the glucohomeostatic needs (17,19,20) and (b) the portal vein blood contains high concentrations of metabolites of intestinal origin (i.e., glucose, lactate, amino acids) as well as a high concentration of immunosuppressive drugs (cyclosporin A, prednisone, azathioprine) administered orally, which may have a toxic effect on the ␤-cell function (19,21,22). Re-innervation by autonomic fibers and neovascularization through the hepatic artery have been shown to take place ‫ف‬ 4-8 wk after transplant in the rodent (23,24).…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

Luzi

Socci

et al. 1996

J. Clin. Invest.

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The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: ( a ) the basal hepatic glucose production; ( b ) the whole body glucose homeostasis and insulin action; and ( c ) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent:

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Effect of Cyclosporin-A on Insulin Secretion in Vitro

Abstract: Fig. 1 Effect of Cyclosporin-A on glucose-induced (20 mmol/l) insulin secretion of isolated rat islets incubated for 180 min.

Cited by 14 publications

References 1 publication

Effects of Cyclosporine on Glucose Tolerance in the Rat

Effects of Cyclosporine on Glucose Tolerance in the Rat

Intravenous Glucose Tolerance and Pancreatic Islet β-Cell Function in Patients With Multiple Sclerosis During 2-yr Treatment With Cyclosporin

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

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