Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression

Molecules

Mats Wiedemann³  Carmen M. Gurrola-D໚z¹  Belinda Vargas-Guerrero¹  Michael Wink⁴  Pedro M. Garc໚-López²  Martina Dﳾr³ 

[1] Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico; E-Mails:;Departamento de Botánica y Zoología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, 45110 Guadalajara, Jalisco, Mexico; E-Mail:;Department of Pharmaceutical and Medicinal Chemistry, Münster University, Corrensstraße 48, 48149 Münster, Germany; E-Mail:;Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg 69120, Germany; E-Mail:

关键词: quinolizidine alkaloids;    beta-cell;    insulin secretion;    K_ATP channel;    lupanine;    Lupinus;    membrane potential;    glucose tolerance;    streptozotocin;    type-2 diabetes mellitus;   

DOI  :  10.3390/molecules201019085

来源: mdpi

【 摘 要 】

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca²⁺ action potentials. Determination of the current through ATP-dependent K⁺ channels (K_ATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the K_ATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.