title: Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.
abstract: 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 beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta 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.
authors.affiliation: Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lindley
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: C
authors.initials: C
authors.lastname: Kane
authors.forename: R M
authors.initials: RM
authors.lastname: Shepherd
authors.forename: P E
authors.initials: PE
authors.lastname: Squires
authors.forename: R F
authors.initials: RF
authors.lastname: James
authors.forename: P R
authors.initials: PR
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Eckhardt
authors.forename: E
authors.initials: E
authors.lastname: Wakeling
authors.forename: M
authors.initials: M
authors.lastname: Dattani
authors.forename: P J
authors.initials: PJ
authors.lastname: Milla
authors.forename: A
authors.initials: A
authors.lastname: Aynsley-Green
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D009543:Nifedipine / Q000627:therapeutic use*; D010182:Pancreatic Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D018408:Patch-Clamp Techniques
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009543:Nifedipine