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Valproic acid modulates islet cell insulin secretion: a possible mechanism of weight gain in epilepsy patients.
Luef, GJ; Lechleitner, M; Bauer, G; Trinka, E; Hengster, P;
Epilepsy Res. 2003; 55(1-2):53-58
Full papers/articles (Journal)


Trinka Eugen


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 drag, 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. (C) 2003 Elsevier B.V. All rights reserved.

Useful keywords (using NLM MeSH Indexing)

Cells, Cultured

Dose-Response Relationship, Drug

Epilepsy/drug therapy*





Islets of Langerhans/drug effects*

Islets of Langerhans/metabolism

Islets of Langerhans/secretion

Pancreas/drug effects



Valproic Acid/pharmacology*

Valproic Acid/therapeutic use

Weight Gain/drug effects*

Weight Gain/physiology

Find related publications in this database (Keywords)

valproic acid
weight gain