title: Valproic acid modulates islet cell insulin secretion: a possible mechanism of weight gain in epilepsy patients.
abstract: A significant weight gain in the course of treatment of epilepsy with valproic acid (VPA) was described in several clinical studies. We recently demonstrated that postprandial insulin levels are increased in patients with VPA therapy. This possible modulation of pancreatic insulin secretion by VPA could be due to the structure of VPA as a fatty acid derivative and thus to direct stimulation of pancreatic insulin secretion or competition with free fatty acids (FFA) for albumin binding. In order to investigate the effect of VPA on insulin secretion in pancreatic islet cells we performed in vitro experiments with islets from pancreases of multiorgan donors. After preparation, the incubation with valproate caused a time and dose-dependent increase of insulin concentration in the cell supernatant. This could also be demonstrated with the control drug, lorazepam, a benzodiazepine, but not with mirtazepin and phenytoin. It can be speculated that an increase in pancreatic insulin secretion under chronic VPA treatment enhances appetite and energy storage and is related to the observed weight gain.
authors.affiliation: Departments of Neurology and Internal Medicine, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. gerhard.luef@uibk.ac.at
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Luef
authors.forename: Monika
authors.initials: M
authors.lastname: Lechleitner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bauer
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.forename: Paul
authors.initials: P
authors.lastname: Hengster
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D007328:Insulin; D014635:Valproic Acid