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Nguyen Khanh Hoa Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Åke Norberg Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Rannar Sillard Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Dao Van Phan Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Nguyen Duy Thuan Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Dang Thi Ngoc Dzung Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Hans Jörnvall Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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Claes-Göran Östenson Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Institute of Material Medica, Hanoi, Vietnam
Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

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We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.

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