Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.

This study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. Treatment of Sprague-Dawley rats with nicotine (3 mg/kg/day) for 6 weeks reduced 43% body weight gain and 65% blood insulin level, but had no effect on blood glucose level. Both insulin...

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Autores principales:	Tian-Ying Xu, Ling-Ling Guo, Pei Wang, Jie Song, Ying-Ying Le, Benoit Viollet, Chao-Yu Miao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62f2afa5fd794069b502659f445fc55e
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spelling	oai:doaj.org-article:62f2afa5fd794069b502659f445fc55e2021-11-18T08:05:24ZChronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.1932-620310.1371/journal.pone.0051217https://doaj.org/article/62f2afa5fd794069b502659f445fc55e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251458/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203This study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. Treatment of Sprague-Dawley rats with nicotine (3 mg/kg/day) for 6 weeks reduced 43% body weight gain and 65% blood insulin level, but had no effect on blood glucose level. Both insulin tolerance test and glucose tolerance test demonstrated that nicotine treatment enhanced insulin sensitivity. Pretreatment of rats with hexamethonium (20 mg/kg/day) to antagonize peripheral nicotinic receptors except for α7 nicotinic acetylcholine receptor (α7-nAChR) had no effect on the insulin sensitizing effect of nicotine. However, the insulin sensitizing effect but not the bodyweight reducing effect of nicotine was abrogated in α7-nAChR knockout mice. Further, chronic treatment with PNU-282987 (0.53 mg/kg/day), a selective α7-nAChR agonist, significantly enhanced insulin sensitivity without apparently modifying bodyweight not only in normal mice but also in AMP-activated kinase-α2 knockout mice, an animal model of insulin resistance with no sign of inflammation. Moreover, PNU-282987 treatment enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in skeletal muscle, adipose tissue and liver in normal mice. PNU-282987 treatment also increased glucose uptake by 25% in C2C12 myotubes and this effect was total abrogated by STAT3 inhibitor, S3I-201. All together, these findings demonstrated that nicotine enhanced insulin sensitivity in animals with or without insulin resistance, at least in part via stimulating α7-nAChR-STAT3 pathway independent of inflammation. Our results contribute not only to the understanding of the pharmacological effects of nicotine, but also to the identifying of new therapeutic targets against insulin resistance.Tian-Ying XuLing-Ling GuoPei WangJie SongYing-Ying LeBenoit ViolletChao-Yu MiaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51217 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tian-Ying Xu Ling-Ling Guo Pei Wang Jie Song Ying-Ying Le Benoit Viollet Chao-Yu Miao Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
description	This study was to investigate the effect of nicotine on insulin sensitivity and explore the underlying mechanisms. Treatment of Sprague-Dawley rats with nicotine (3 mg/kg/day) for 6 weeks reduced 43% body weight gain and 65% blood insulin level, but had no effect on blood glucose level. Both insulin tolerance test and glucose tolerance test demonstrated that nicotine treatment enhanced insulin sensitivity. Pretreatment of rats with hexamethonium (20 mg/kg/day) to antagonize peripheral nicotinic receptors except for α7 nicotinic acetylcholine receptor (α7-nAChR) had no effect on the insulin sensitizing effect of nicotine. However, the insulin sensitizing effect but not the bodyweight reducing effect of nicotine was abrogated in α7-nAChR knockout mice. Further, chronic treatment with PNU-282987 (0.53 mg/kg/day), a selective α7-nAChR agonist, significantly enhanced insulin sensitivity without apparently modifying bodyweight not only in normal mice but also in AMP-activated kinase-α2 knockout mice, an animal model of insulin resistance with no sign of inflammation. Moreover, PNU-282987 treatment enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in skeletal muscle, adipose tissue and liver in normal mice. PNU-282987 treatment also increased glucose uptake by 25% in C2C12 myotubes and this effect was total abrogated by STAT3 inhibitor, S3I-201. All together, these findings demonstrated that nicotine enhanced insulin sensitivity in animals with or without insulin resistance, at least in part via stimulating α7-nAChR-STAT3 pathway independent of inflammation. Our results contribute not only to the understanding of the pharmacological effects of nicotine, but also to the identifying of new therapeutic targets against insulin resistance.
format	article
author	Tian-Ying Xu Ling-Ling Guo Pei Wang Jie Song Ying-Ying Le Benoit Viollet Chao-Yu Miao
author_facet	Tian-Ying Xu Ling-Ling Guo Pei Wang Jie Song Ying-Ying Le Benoit Viollet Chao-Yu Miao
author_sort	Tian-Ying Xu
title	Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
title_short	Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
title_full	Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
title_fullStr	Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
title_full_unstemmed	Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.
title_sort	chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-stat3 pathway.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/62f2afa5fd794069b502659f445fc55e
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Chronic exposure to nicotine enhances insulin sensitivity through α7 nicotinic acetylcholine receptor-STAT3 pathway.

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