Nuciferine stimulates insulin secretion from beta cells-an in vitro comparison with glibenclamide.
BACKGROUND
Several Asian plants are known for their anti-diabetic properties and produce alkaloids and flavonoids that may stimulate insulin secretion.


METHODS
Using Vietnamese plants (Nelumbo nucifera, Gynostemma pentaphyllum, Smilax glabra, and Stemona tuberosa), we extracted two alkaloids (neotuberostemonine, nuciferine) and four flavonoids (astilbin, engeletin, smitilbin, and 3,5,3'-trihydroxy-7,4'-dimethoxyflavone), and studied their insulin stimulatory effects.


RESULTS
Nuciferine, extracted from Nelumbo nucifera, stimulated both phases of insulin secretion in isolated islets, whereas the other compounds had no effect. The effect of nuciferine was totally abolished by diazoxide and nimodipine, and diminished by protein kinase A and protein kinase C inhibition. Nuciferine and potassium had additive effects on insulin secretion. Nuciferine also stimulated insulin secretion in INS-1E cells at both 3.3 and 16.7 mM glucose concentrations. Compared with glibenclamide, nuciferine had a stronger effect on insulin secretion and less beta-cell toxicity. However, nuciferine did not compete with glibenclamide for binding to the sulfonylurea receptor.


CONCLUSIONS
Among several compounds extracted from anti-diabetic plants, nuciferine was found to stimulate insulin secretion by closing potassium-adenosine triphosphate channels, explaining anti-diabetic effects of Nelumbo nucifera.
Department of Physiology, University of Manitoba, Winnipeg, MB, Canada R3E3P4.
K Hoa
KH
Nguyen
T Nhan
TN
Ta
T Hong Minh
TH
Pham
Q Tien
QT
Nguyen
H Dien
HD
Pham
Suresh
S
Mishra
B L Grégoire
BL
Nyomba
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001060:Aporphines / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D051379:Mice; D031653:Nelumbo / Q000737:chemistry*; D009553:Nimodipine / Q000494:pharmacology; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011493:Protein Kinase C / Q000494:pharmacology; D011955:Receptors, Drug / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014744:Vietnam
D018528:ATP-Binding Cassette Transporters; D000959:Antihypertensive Agents; D001060:Aporphines; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D010936:Plant Extracts; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D009553:Nimodipine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D005905:Glyburide; C008692:nuciferine