Limits...
Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma pentaphyllum and the Possible Mechanisms of Insulin Release.

Lokman EF, Gu HF, Wan Mohamud WN, Östenson CG - Evid Based Complement Alternat Med (2015)

Bottom Line: Opening of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP.Conclusion.The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of Gynostemma pentaphyllum (GP) on glucose stimulated insulin secretion from isolated GK rat islets with K-ATP channel opened by diazoxide (D) and depolarized by kalium chloride (KCl). ∗∗∗P < 0.001 (when compared with control group with no addition at 3.3 mM and 16.7 mM glucose); #P < 0.05 (when compared with group with only D + KCl); ¤P < 0.05, ¤¤¤P < 0.001 (when compared with group with only GP); αααP < 0.001 (when compared with D only). Results of insulin release (μU/islet/hour) are the means ± SEM of five independent experiments with three replicates for each experiment.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4493304&req=5

fig3: Effects of Gynostemma pentaphyllum (GP) on glucose stimulated insulin secretion from isolated GK rat islets with K-ATP channel opened by diazoxide (D) and depolarized by kalium chloride (KCl). ∗∗∗P < 0.001 (when compared with control group with no addition at 3.3 mM and 16.7 mM glucose); #P < 0.05 (when compared with group with only D + KCl); ¤P < 0.05, ¤¤¤P < 0.001 (when compared with group with only GP); αααP < 0.001 (when compared with D only). Results of insulin release (μU/islet/hour) are the means ± SEM of five independent experiments with three replicates for each experiment.

Mentions: The closure of K-ATP channels in pancreatic  β-cells leads to membrane depolarization and the stimulation of insulin release. Therefore, to understand if GP stimulates insulin release via the K-ATP channels, we used diazoxide. The addition of diazoxide inhibits insulin release by opening the K-ATP channels in pancreatic  β-cells [24]. KCl was used for membrane depolarization. GP significantly increased insulin release 3.4-fold (P < 0.001) compared to the control group at 16.7 mM glucose (Figure 3). The opening of K-ATP channels by adding diazoxide (0.25 mM) inhibited insulin release by 63% at 16.7 mM glucose. In addition, at 16.7 mM glucose, diazoxide decreased insulin response to GP from 78.1 ± 15.6 to 26 ± 17.0 μU/islet/hour (P < 0.001). The addition of potassium chloride (KCl) to islets incubated with diazoxide to depolarize the  β-cells increased insulin release at both 3.3 mM and 16.7 mM glucose compared to the control group. At 16.7 mM, the insulin response to GP + diazoxide and KCl was significantly higher compared to islets incubated with diazoxide + KCl (at P < 0.05).


Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma pentaphyllum and the Possible Mechanisms of Insulin Release.

Lokman EF, Gu HF, Wan Mohamud WN, Östenson CG - Evid Based Complement Alternat Med (2015)

Effects of Gynostemma pentaphyllum (GP) on glucose stimulated insulin secretion from isolated GK rat islets with K-ATP channel opened by diazoxide (D) and depolarized by kalium chloride (KCl). ∗∗∗P < 0.001 (when compared with control group with no addition at 3.3 mM and 16.7 mM glucose); #P < 0.05 (when compared with group with only D + KCl); ¤P < 0.05, ¤¤¤P < 0.001 (when compared with group with only GP); αααP < 0.001 (when compared with D only). Results of insulin release (μU/islet/hour) are the means ± SEM of five independent experiments with three replicates for each experiment.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493304&req=5

fig3: Effects of Gynostemma pentaphyllum (GP) on glucose stimulated insulin secretion from isolated GK rat islets with K-ATP channel opened by diazoxide (D) and depolarized by kalium chloride (KCl). ∗∗∗P < 0.001 (when compared with control group with no addition at 3.3 mM and 16.7 mM glucose); #P < 0.05 (when compared with group with only D + KCl); ¤P < 0.05, ¤¤¤P < 0.001 (when compared with group with only GP); αααP < 0.001 (when compared with D only). Results of insulin release (μU/islet/hour) are the means ± SEM of five independent experiments with three replicates for each experiment.
Mentions: The closure of K-ATP channels in pancreatic  β-cells leads to membrane depolarization and the stimulation of insulin release. Therefore, to understand if GP stimulates insulin release via the K-ATP channels, we used diazoxide. The addition of diazoxide inhibits insulin release by opening the K-ATP channels in pancreatic  β-cells [24]. KCl was used for membrane depolarization. GP significantly increased insulin release 3.4-fold (P < 0.001) compared to the control group at 16.7 mM glucose (Figure 3). The opening of K-ATP channels by adding diazoxide (0.25 mM) inhibited insulin release by 63% at 16.7 mM glucose. In addition, at 16.7 mM glucose, diazoxide decreased insulin response to GP from 78.1 ± 15.6 to 26 ± 17.0 μU/islet/hour (P < 0.001). The addition of potassium chloride (KCl) to islets incubated with diazoxide to depolarize the  β-cells increased insulin release at both 3.3 mM and 16.7 mM glucose compared to the control group. At 16.7 mM, the insulin response to GP + diazoxide and KCl was significantly higher compared to islets incubated with diazoxide + KCl (at P < 0.05).

Bottom Line: Opening of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP.Conclusion.The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus