Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion

• Published in: European journal of pharmacology 2004-11, Vol.504 (1), p.139-142
• Main Authors: García López, Pedro M., de la Mora, P. Garzón, Wysocka, W., Maiztegui, Bárbara, Alzugaray, María E., Del Zotto, Héctor, Borelli, María I.
• Format: Article
• Language: English
• Subjects: Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Biological and medical sciences; Insulin - metabolism; Insulin Secretion; Islet; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; K ATP channel; Lupinus; Male; Medical sciences; Pharmacology. Drug treatments; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Quinolizidine alkaloid; Quinolizines - isolation & purification; Quinolizines - pharmacology; Rats; Rats, Wistar
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.09.008

We have analyzed the effect of quinolizidine alkaloids from Lupinus species upon insulin secretion. Isolated normal rat islets were incubated with 3.3, 8.3, and 16.7 mM glucose, in the presence or absence of different concentrations of lupanine (0.05, 0.5, and 1.0 mM), 13-α-OH lupanine, 17-oxo-lupanine, and 2-thionosparteine. Insulin release was measured by radioimmunoassay. While 2-thionosparteine enhanced insulin secretion at all glucose concentrations, lupanine did at 8.3 and 16.7 mM, and 13-α-OH lupanine or 17-oxo-lupanine only at 16.7 mM glucose. Diazoxide (0.1 mM) decreased the effect of all alkaloids, without suppressing it completely. Consequently, blockage of β-cell K ATP-sensitive channels is at least one of the mechanisms involved in the enhancing secretagogue effects of quinolizidine alkaloids. The fact that 13-α-OH lupanine and 17-oxo-lupanine only exert their secretagogue effect at high glucose concentrations could be of additional value when considering their potential use in the treatment of type 2 diabetes.