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Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells
Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose ti...
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Published in: | PloS one 2017-04, Vol.12 (4), p.e0175498 |
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description | Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells. |
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Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0175498</identifier><identifier>PMID: 28394923</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipose tissue ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Bcl protein ; Bcl-2 protein ; Bcl-x protein ; Biology and Life Sciences ; Blood ; Blood glucose ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Body weight ; Body Weight - drug effects ; Body Weight - physiology ; Cell growth ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Proliferation - physiology ; Cells, Cultured ; Cytokines ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Energy expenditure ; Fibronectins - administration & dosage ; Fibronectins - metabolism ; Glucose ; Glucose tolerance ; Glucose Tolerance Test ; Hypoglycemic Agents - administration & dosage ; Insulin ; Insulin resistance ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Male ; MAP kinase ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Medicine and Health Sciences ; Pancreas ; Physical Sciences ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Secretion ; Studies ; Thermogenesis ; Toxicity</subject><ispartof>PloS one, 2017-04, Vol.12 (4), p.e0175498</ispartof><rights>2017 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Liu et al 2017 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-60d1310feed608e0f02910ff315924bc5eb31e372747e07f280aa497717f9c163</citedby><cites>FETCH-LOGICAL-c526t-60d1310feed608e0f02910ff315924bc5eb31e372747e07f280aa497717f9c163</cites><orcidid>0000-0002-7816-3091</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1886286802/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1886286802?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28394923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xu, Shang-Zhong</contributor><creatorcontrib>Liu, Shiwei</creatorcontrib><creatorcontrib>Du, Fang</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Wang, Mingming</creatorcontrib><creatorcontrib>Duan, Ruixue</creatorcontrib><creatorcontrib>Zhang, Jiaxin</creatorcontrib><creatorcontrib>Wu, Yaru</creatorcontrib><creatorcontrib>Zhang, Qi</creatorcontrib><title>Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.</description><subject>Adipose tissue</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Bcl protein</subject><subject>Bcl-2 protein</subject><subject>Bcl-x protein</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Blood glucose</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Body weight</subject><subject>Body Weight - drug effects</subject><subject>Body Weight - physiology</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - physiology</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Energy expenditure</subject><subject>Fibronectins - administration & dosage</subject><subject>Fibronectins - metabolism</subject><subject>Glucose</subject><subject>Glucose tolerance</subject><subject>Glucose Tolerance Test</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Male</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Medicine and Health Sciences</subject><subject>Pancreas</subject><subject>Physical Sciences</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Secretion</subject><subject>Studies</subject><subject>Thermogenesis</subject><subject>Toxicity</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1UstuFDEQtBARCYE_QGCJ8278GL8uSCgKECkSl-RseT3tXa9m7cGeRcpv8SF8E97sJEoOnNzurqoudTdCHyhZUq7oxTbvS3LDcswJloQq0Rn9Cp1Rw9lCMsJfP4tP0dtat4QIrqV8g06Z5qYzjJ8huAoB_FSxSz3epx7KcB_TGu_Ab1yKdVdxDjiWWGPCOeFpA3gseYgBiptiyxyIbszjlGt8AI8u-QKt6PHfP9jDMNR36CS4ocL7-T1Hd9-ubi9_LG5-fr--_Hqz8ILJaSFJTzklAaCXRAMJhJn2DZwKw7qVF7DiFLhiqlNAVGCaONcZpagKxlPJz9Gno-445GrnCVVLtZZMS01YQ1wfEX12WzuWuHPl3mYX7UMil7V1pVkfwDIFjPZtZibQbiWCFkSwTveCGHBciqb1Ze62X-2g95Cm4oYXoi8rKW7sOv-2hzUwZZrA51mg5F97qNN_LHdHlC-51gLhqQMl9nAKjyx7OAU7n0KjfXzu7on0uHv-DxR7syw</recordid><startdate>20170410</startdate><enddate>20170410</enddate><creator>Liu, Shiwei</creator><creator>Du, Fang</creator><creator>Li, Xin</creator><creator>Wang, Mingming</creator><creator>Duan, Ruixue</creator><creator>Zhang, Jiaxin</creator><creator>Wu, Yaru</creator><creator>Zhang, Qi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7816-3091</orcidid></search><sort><creationdate>20170410</creationdate><title>Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells</title><author>Liu, Shiwei ; Du, Fang ; Li, Xin ; Wang, Mingming ; Duan, Ruixue ; Zhang, Jiaxin ; Wu, Yaru ; Zhang, Qi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-60d1310feed608e0f02910ff315924bc5eb31e372747e07f280aa497717f9c163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adipose tissue</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - 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Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28394923</pmid><doi>10.1371/journal.pone.0175498</doi><orcidid>https://orcid.org/0000-0002-7816-3091</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adipose tissue Animals Apoptosis Apoptosis - drug effects Apoptosis - physiology Bcl protein Bcl-2 protein Bcl-x protein Biology and Life Sciences Blood Blood glucose Blood Glucose - drug effects Blood Glucose - metabolism Body weight Body Weight - drug effects Body Weight - physiology Cell growth Cell proliferation Cell Proliferation - drug effects Cell Proliferation - physiology Cells, Cultured Cytokines Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Energy expenditure Fibronectins - administration & dosage Fibronectins - metabolism Glucose Glucose tolerance Glucose Tolerance Test Hypoglycemic Agents - administration & dosage Insulin Insulin resistance Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Male MAP kinase MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Medicine and Health Sciences Pancreas Physical Sciences Random Allocation Rats Rats, Sprague-Dawley Secretion Studies Thermogenesis Toxicity |
title | Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells |
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