Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells

The non-steroidal compound STX modulates the hypothalamic control of core body temperature and energy homeostasis. The aim of this work was to study the potential effects of STX on pancreatic β-cell function. 1–10 nM STX produced an increase in glucose-induced insulin secretion in isolated islets fr...

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Main Authors:	Ropero, Ana B., Alonso-Magdalena, Paloma, Soriano, Sergi, Juan-Picó, Pablo, Roepke, Troy A., Kelly, Martin J., Nadal, Ángel
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323542/

id	pubmed-3323542
recordtype	oai_dc
spelling	pubmed-33235422012-04-13 Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells Ropero, Ana B. Alonso-Magdalena, Paloma Soriano, Sergi Juan-Picó, Pablo Roepke, Troy A. Kelly, Martin J. Nadal, Ángel Research Article The non-steroidal compound STX modulates the hypothalamic control of core body temperature and energy homeostasis. The aim of this work was to study the potential effects of STX on pancreatic β-cell function. 1–10 nM STX produced an increase in glucose-induced insulin secretion in isolated islets from male mice, whereas it had no effect in islets from female mice. This insulinotropic effect of STX was abolished by the anti-estrogen ICI 182,780. STX increased intracellular calcium entry in both whole islets and isolated β-cells, and closed the KATP channel, suggesting a direct effect on β-cells. When intraperitoneal glucose tolerance test was performed, a single dose of 100 µg/kg body weight STX improved glucose sensitivity in males, yet it had a slight effect on females. In agreement with the effect on isolated islets, 100 µg/kg dose of STX enhanced the plasma insulin increase in response to a glucose load, while it did not in females. Long-term treatment (100 µg/kg, 6 days) of male mice with STX did not alter body weight, fasting glucose, glucose sensitivity or islet insulin content. Ovariectomized females were insensitive to STX (100 µg/kg), after either an acute administration or a 6-day treatment. This long-term treatment was also ineffective in a mouse model of mild diabetes. Therefore, STX appears to have a gender-specific effect on blood glucose homeostasis, which is only manifested after an acute administration. The insulinotropic effect of STX in pancreatic β-cells is mediated by the closure of the KATP channel and the increase in intracellular calcium concentration. The in vivo improvement in glucose tolerance appears to be mostly due to the enhancement of insulin secretion from β-cells. Public Library of Science 2012-04-10 /pmc/articles/PMC3323542/ /pubmed/22506040 http://dx.doi.org/10.1371/journal.pone.0034650 Text en Ropero et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ropero, Ana B. Alonso-Magdalena, Paloma Soriano, Sergi Juan-Picó, Pablo Roepke, Troy A. Kelly, Martin J. Nadal, Ángel
spellingShingle	Ropero, Ana B. Alonso-Magdalena, Paloma Soriano, Sergi Juan-Picó, Pablo Roepke, Troy A. Kelly, Martin J. Nadal, Ángel Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
author_facet	Ropero, Ana B. Alonso-Magdalena, Paloma Soriano, Sergi Juan-Picó, Pablo Roepke, Troy A. Kelly, Martin J. Nadal, Ángel
author_sort	Ropero, Ana B.
title	Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
title_short	Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
title_full	Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
title_fullStr	Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
title_full_unstemmed	Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells
title_sort	insulinotropic effect of the non-steroidal compound stx in pancreatic β-cells
description	The non-steroidal compound STX modulates the hypothalamic control of core body temperature and energy homeostasis. The aim of this work was to study the potential effects of STX on pancreatic β-cell function. 1–10 nM STX produced an increase in glucose-induced insulin secretion in isolated islets from male mice, whereas it had no effect in islets from female mice. This insulinotropic effect of STX was abolished by the anti-estrogen ICI 182,780. STX increased intracellular calcium entry in both whole islets and isolated β-cells, and closed the KATP channel, suggesting a direct effect on β-cells. When intraperitoneal glucose tolerance test was performed, a single dose of 100 µg/kg body weight STX improved glucose sensitivity in males, yet it had a slight effect on females. In agreement with the effect on isolated islets, 100 µg/kg dose of STX enhanced the plasma insulin increase in response to a glucose load, while it did not in females. Long-term treatment (100 µg/kg, 6 days) of male mice with STX did not alter body weight, fasting glucose, glucose sensitivity or islet insulin content. Ovariectomized females were insensitive to STX (100 µg/kg), after either an acute administration or a 6-day treatment. This long-term treatment was also ineffective in a mouse model of mild diabetes. Therefore, STX appears to have a gender-specific effect on blood glucose homeostasis, which is only manifested after an acute administration. The insulinotropic effect of STX in pancreatic β-cells is mediated by the closure of the KATP channel and the increase in intracellular calcium concentration. The in vivo improvement in glucose tolerance appears to be mostly due to the enhancement of insulin secretion from β-cells.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323542/
_version_	1611520215597711360

Insulinotropic Effect of the Non-Steroidal Compound STX in Pancreatic β-Cells

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