The protective effect of verapamil on mouse islets transplanted under the kidney capsule

Islets from normal NMRI mice were transplanted under the kidney capsule of syngeneic recipients. The graft-bearing mice were divided into 4 groups treated daily with cremophor alone (control), cyclosporine (25 mg/kg body wt), CsA in combination with the calcium antagonist verapamil (0.4 mg/kg), or verapamil alone. After 3 weeks the grafts were removed, analyzed for insulin secretory dynamics in a perifusion system, and extracted for their contents of insulin. The graft insulin content was significantly decreased by CsA, an effect counteracted by verapamil. As compared with controls, all treatments increased the basal insulin at 2.8 mmol/L glucose. CsA together with verapamil enhanced the biphasic secretory response to 16.7 mmol/L glucose, whether expressed per graft or per unit of insulin content. The glucose-stimulated insulin release per graft was greater after combining CsA with verapamil than after CsA alone. It is concluded that CsA has adverse effects on islets transplanted to the kidney, and that these effects can be ameliorated by combining the immunosuppressant with verapamil.