title: Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway.
abstract: To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-dependent manner. In addition, 4.5 micromol/l RSG potentiated the glucose (10 mmol/l)-induced insulin secretion. Both the first and second phases of glucose-induced insulin secretion were significantly enhanced by RSG, by 80.7 and 52.4%, respectively. The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In contrast, the glucose-stimulated insulin secretion was not affected by LY294002. The potentiation effect of RSG on glucose-stimulated insulin secretion, in both the first and second phases, was significantly blocked by LY294002. These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. The inability of LY294002 to inhibit glucose-induced insulin secretion suggests that different pathways are responsible for glucose and RSG signaling.
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: T J
authors.initials: TJ
authors.lastname: Chang
authors.forename: J C
authors.initials: JC
authors.lastname: Chang
authors.forename: M W
authors.initials: MW
authors.lastname: Liu
authors.forename: T Y
authors.initials: TY
authors.lastname: Tai
authors.forename: W H
authors.initials: WH
authors.lastname: Hsu
authors.forename: L M
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose