IONIC CONTROL OF BETA-CELL FUNCTION IN NESIDIOBLASTOSIS - A POSSIBLE THERAPEUTIC ROLE FOR CALCIUM-CHANNEL BLOCKADE

A preterm female infant presented with intractable hypoglycaemia withi n 10 minutes of delivery. Normoglycaemia could be maintained only by t he intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persi stent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose <0.5 mmol/l). Medical treatment w ith glucagon, somatostatin, and diazoxide led to only a modest reducti on in the intravenous glucose requirement; a 95% pancreatectomy was pe rformed and histological 'nesidioblastosis' confirmed. In vitro electr ophysiological studies using patch clamp techniques on isolated pancre atic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient gluc ose concentrations with persistently firing action potentials; these w ere blocked reversibly by the calcium channel blocking agent verapamil . Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrati ons from 3.5 to 4.8 mmol/l and increased in duration the child's toler ance to fasting from 3 to 10.5 hours. These data allude to an abnormal ity in the ionic control of insulin release in nesidioblastosis and of fer a new logical approach to treatment which requires further evaluat ion.