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Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression

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 perform...

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Autores principales: Wiedemann, Mats, Gurrola-Díaz, Carmen M., Vargas-Guerrero, Belinda, Wink, Michael, García-López, Pedro M., Düfer, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332548/
https://www.ncbi.nlm.nih.gov/pubmed/26492234
http://dx.doi.org/10.3390/molecules201019085
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author Wiedemann, Mats
Gurrola-Díaz, Carmen M.
Vargas-Guerrero, Belinda
Wink, Michael
García-López, Pedro M.
Düfer, Martina
author_facet Wiedemann, Mats
Gurrola-Díaz, Carmen M.
Vargas-Guerrero, Belinda
Wink, Michael
García-López, Pedro M.
Düfer, Martina
author_sort Wiedemann, Mats
collection PubMed
description 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 Ca(2+) 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.
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spelling pubmed-63325482019-01-24 Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression Wiedemann, Mats Gurrola-Díaz, Carmen M. Vargas-Guerrero, Belinda Wink, Michael García-López, Pedro M. Düfer, Martina Molecules Article 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 Ca(2+) 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. MDPI 2015-10-20 /pmc/articles/PMC6332548/ /pubmed/26492234 http://dx.doi.org/10.3390/molecules201019085 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wiedemann, Mats
Gurrola-Díaz, Carmen M.
Vargas-Guerrero, Belinda
Wink, Michael
García-López, Pedro M.
Düfer, Martina
Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title_full Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title_fullStr Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title_full_unstemmed Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title_short Lupanine Improves Glucose Homeostasis by Influencing K(ATP) Channels and Insulin Gene Expression
title_sort lupanine improves glucose homeostasis by influencing k(atp) channels and insulin gene expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332548/
https://www.ncbi.nlm.nih.gov/pubmed/26492234
http://dx.doi.org/10.3390/molecules201019085
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