Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells

Eugenosedin-A (Eu-A) has been shown to protect against hyperglycemia- and hyperlipidemia-induced metabolic syndrome. We investigated the relationship of KATP channel activities and insulin secretion by Eu-A in vitro in pancreatic β-cells, and examined the effect of Eu-A on streptozotocin (STZ)/nicot...

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Autores principales:	Rong-Jyh Lin, Yu-Kwan Yen, Chien-Hsing Lee, Su-Ling Hsieh, Yu-Chin Chang, Yung-Shun Juan, Cheng-Yu Long, Kuo-Ping Shen, Bin-Nan Wu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Eugenosedin-A Pancreatic β-cells KATP channels Perforated patch-clamp Type 2 diabetes mellitus Kir6.2 proteins Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/fcf8942b922c46c5bf6023f97beb461e
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spelling	oai:doaj.org-article:fcf8942b922c46c5bf6023f97beb461e2021-11-22T04:17:52ZEugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells0753-332210.1016/j.biopha.2021.112447https://doaj.org/article/fcf8942b922c46c5bf6023f97beb461e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012336https://doaj.org/toc/0753-3322Eugenosedin-A (Eu-A) has been shown to protect against hyperglycemia- and hyperlipidemia-induced metabolic syndrome. We investigated the relationship of KATP channel activities and insulin secretion by Eu-A in vitro in pancreatic β-cells, and examined the effect of Eu-A on streptozotocin (STZ)/nicotinamide (NA)-induced type 2 diabetes mellitus (T2DM) in vivo. We isolated pancreatic islets from adult male Wistar rats (250–350 g) and identified pancreatic β-cells by the cell size, capacitance and membrane potential. Perforated patch-clamp and inside-out recordings were used to monitor the membrane potential (current-clamp mode) and channel activity (voltage-clamp mode) of β-cells. The membrane potential of β-cells was raised by Eu-A and reversed by the KATP channel activator diazoxide. Eu-A inhibited the KATP channel activity measured at − 60 mV and increased the intracellular calcium concentration ([Ca2+]i), resulting in enhanced insulin secretion. Eu-A also reduced Kir6.2 protein on the cell membrane and scattered in the cytosol under normal glucose conditions (5.6 mM). In our animal study, rats were divided into normal and STZ/NA-induced T2DM groups. Normal rats fed with regular chow were divided into control and control+Eu-A (5 mg/kg/day, i.p.) groups. The STZ/NA-induced diabetic rats fed with a high-fat diet (HFD) were divided into three groups: T2DM, T2DM+Eu-A (5 mg/kg/day, i.p.), and T2DM+glibenclamide (0.5 mg/kg/day, i.p.; a KATP channel inhibitor). Both Eu-A and glibenclamide decreased the rats’ blood glucose, prevented weight gain, and enhanced insulin secretion. We found that Eu-A blocked pancreatic β-cell KATP channels, caused membrane potential depolarization, and stimulated Ca2+ influx, thus increasing insulin secretion. Furthermore, Eu-A decreased blood glucose and increased insulin levels in T2DM rats. These results suggested that Eu-A might have clinical benefits for the control of T2DM and its complications.Rong-Jyh LinYu-Kwan YenChien-Hsing LeeSu-Ling HsiehYu-Chin ChangYung-Shun JuanCheng-Yu LongKuo-Ping ShenBin-Nan WuElsevierarticleEugenosedin-APancreatic β-cellsKATP channelsPerforated patch-clampType 2 diabetes mellitusKir6.2 proteinsTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112447- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Eugenosedin-A Pancreatic β-cells KATP channels Perforated patch-clamp Type 2 diabetes mellitus Kir6.2 proteins Therapeutics. Pharmacology RM1-950
spellingShingle	Eugenosedin-A Pancreatic β-cells KATP channels Perforated patch-clamp Type 2 diabetes mellitus Kir6.2 proteins Therapeutics. Pharmacology RM1-950 Rong-Jyh Lin Yu-Kwan Yen Chien-Hsing Lee Su-Ling Hsieh Yu-Chin Chang Yung-Shun Juan Cheng-Yu Long Kuo-Ping Shen Bin-Nan Wu Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
description	Eugenosedin-A (Eu-A) has been shown to protect against hyperglycemia- and hyperlipidemia-induced metabolic syndrome. We investigated the relationship of KATP channel activities and insulin secretion by Eu-A in vitro in pancreatic β-cells, and examined the effect of Eu-A on streptozotocin (STZ)/nicotinamide (NA)-induced type 2 diabetes mellitus (T2DM) in vivo. We isolated pancreatic islets from adult male Wistar rats (250–350 g) and identified pancreatic β-cells by the cell size, capacitance and membrane potential. Perforated patch-clamp and inside-out recordings were used to monitor the membrane potential (current-clamp mode) and channel activity (voltage-clamp mode) of β-cells. The membrane potential of β-cells was raised by Eu-A and reversed by the KATP channel activator diazoxide. Eu-A inhibited the KATP channel activity measured at − 60 mV and increased the intracellular calcium concentration ([Ca2+]i), resulting in enhanced insulin secretion. Eu-A also reduced Kir6.2 protein on the cell membrane and scattered in the cytosol under normal glucose conditions (5.6 mM). In our animal study, rats were divided into normal and STZ/NA-induced T2DM groups. Normal rats fed with regular chow were divided into control and control+Eu-A (5 mg/kg/day, i.p.) groups. The STZ/NA-induced diabetic rats fed with a high-fat diet (HFD) were divided into three groups: T2DM, T2DM+Eu-A (5 mg/kg/day, i.p.), and T2DM+glibenclamide (0.5 mg/kg/day, i.p.; a KATP channel inhibitor). Both Eu-A and glibenclamide decreased the rats’ blood glucose, prevented weight gain, and enhanced insulin secretion. We found that Eu-A blocked pancreatic β-cell KATP channels, caused membrane potential depolarization, and stimulated Ca2+ influx, thus increasing insulin secretion. Furthermore, Eu-A decreased blood glucose and increased insulin levels in T2DM rats. These results suggested that Eu-A might have clinical benefits for the control of T2DM and its complications.
format	article
author	Rong-Jyh Lin Yu-Kwan Yen Chien-Hsing Lee Su-Ling Hsieh Yu-Chin Chang Yung-Shun Juan Cheng-Yu Long Kuo-Ping Shen Bin-Nan Wu
author_facet	Rong-Jyh Lin Yu-Kwan Yen Chien-Hsing Lee Su-Ling Hsieh Yu-Chin Chang Yung-Shun Juan Cheng-Yu Long Kuo-Ping Shen Bin-Nan Wu
author_sort	Rong-Jyh Lin
title	Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
title_short	Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
title_full	Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
title_fullStr	Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
title_full_unstemmed	Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells
title_sort	eugenosedin-a improves obesity-related hyperglycemia by regulating atp-sensitive k+ channels and insulin secretion in pancreatic β cells
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/fcf8942b922c46c5bf6023f97beb461e
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Eugenosedin-A improves obesity-related hyperglycemia by regulating ATP-sensitive K+ channels and insulin secretion in pancreatic β cells

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