THE PROTECTIVE EFFECT OF VERAPAMIL ON MOUSE ISLETS TRANSPLANTED UNDERTHE KIDNEY CAPSULE

Islets from normal NMRI mice were transplanted under the kidney capsul e 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 verapam il (0.4 mg/kg), or verapamil alone. After 3 weeks the grafts were remo ved, analyzed for insulin secretory dynamics in a perifusion system, a nd extracted for their contents of insulin. The graft insulin content was significantly decreased by CsA, an effect counteracted by verapami l. As compared with controls, all treatments increased the basal insul in at 2.8 mmol/L glucose. CsA together with verapamil enhanced the bip hasic 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 islet s transplanted to the kidney, and that these effects can be ameliorate d by combining the immunosuppressant with verapamil.