title: Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma pentaphyllum and the Possible Mechanisms of Insulin Release.
abstract: Aims. To evaluate the antidiabetic effects of Gynostemma pentaphyllum (GP) in Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, and to investigate the mechanisms of insulin release. Methods. Oral glucose tolerance test was performed and plasma insulin levels were measured. Results. An oral treatment with GP (0.3 g/kg of body weight daily) for two weeks in GK rats improved glucose tolerance versus placebo group (P < 0.01). Plasma insulin levels were significantly increased in the GP-treated group. The insulin release from GP-treated GK rats was 1.9-fold higher as compared to the control group (P < 0.001). GP stimulated insulin release in isolated GK rat islets at high glucose. Opening of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP. Furthermore, the protein kinase A (PKA) inhibitor H89 decreased the insulin response to GP (P < 0.05). In addition, GP-induced insulin secretion was decreased after preincubation of GK islets with pertussis toxin to inhibit exocytotic Ge proteins (P < 0.05). Conclusion. The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets. GP-induced insulin release is partly mediated via K-ATP and L-type Ca(2+) channels, the PKA system and also dependent on pertussis toxin sensitive Ge-protein.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden ; Diabetes and Endocrine Unit, Cardiovascular, Diabetes and Nutrition Research Centre (CDNRC), Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Ezarul Faradianna
authors.initials: EF
authors.lastname: Lokman
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Harvest F
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Diabetes and Endocrine Unit, Cardiovascular, Diabetes and Nutrition Research Centre (CDNRC), Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Wan Nazaimoon
authors.initials: WN
authors.lastname: Wan Mohamud
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Östenson