Cyclosporin A and islet function.

Long-term cyclosporin A (CsA) administration in dogs was studied with respect to function of the islets of Langerhans. After 3 weeks of immunosuppression with therapeutic doses, the islets were isolated and assessed in vitro for insulin release in response to glucose challenge. Islet tissue retrieved from the CsA-treated animals showed a total insulin output significantly lower than that of the control animals (p less than 0.01). The first and second phases of insulin release were both impaired in animals treated with CsA compared with controls (p less than 0.001 and p less than 0.05, respectively). The negative impact of CsA on the beta cells was easily demonstrated in this in vitro study. Similar results are more difficult to achieve with purely in vivo models, probably due to the great redundancy of the islet mass in intact animals. The mechanism of this CsA toxicity remains to be defined.