Ionic control of β cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade

Lindley, K. J., Dunne, M. J., Kane, C. , Shepherd, R. M., Squires, Paul, James, R. F. L., Johnson, P. R. V., Eckhardt, S., Wakeling, E., Dattani, M., Milla, P. J. and Aynsley-Green, A. (1996) Ionic control of β cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade. Archives of Disease in Childhood, 74 (3 SUPP). pp. 373-378. ISSN 0003-9888

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Item Type:Article
Item Status:Live Archive


A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent 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 with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95 pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic β cells characterised the ionic basis for insulin secretion in nesidioblastosis. The β cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.

Keywords:calcium channel, diazoxide, glucagon, nifedipine, somatostatin, verapamil, action potential, article, case report, depolarization, female, human, human cell, hypoglycemia, infant, insulin release, insulinoma, intravenous drug administration, ion current, oral drug administration, pancreas islet beta cell, priority journal, Blood Glucose, Calcium Channel Blockers, Calcium Channels, Electrophysiology, Humans, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Islets of Langerhans, Pancreatic Diseases, Patch-Clamp Techniques
Subjects:A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:14471
Deposited On:11 Jul 2014 11:08

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