Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells
Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2012-07, Vol.153 (7), p.3029-3039 |
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| description | Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells. |
| doi_str_mv | 10.1210/en.2012-1091 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3380305</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1210/en.2012-1091</oup_id><sourcerecordid>1660389059</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-1812b6133c7acfcdeb298852eb6f7d13462afb36ee39cc67184ead9fee51c00d3</originalsourceid><addsrcrecordid>eNqFks1u1DAUhSMEotPCjjWyhBAsSPFPYicbpGpUhhFTqErL1nKcm5lUjh3spFK3fSQehGfCYYYWEIiVZfnzuffce5LkCcGHhBL8GuwhxYSmBJfkXjIjZZanggh8P5lhTFgqKBV7yX4Il_GaZRl7mOxRmpciZ_ksuTmyQ6vWrV2jBVhA740bNg4d242yGgJamFG7AOnS1qOGGi1tGE1r0SfQHobWWVRdo4s-PYP1aNQw6ZwaFTqFTqCrvIqSK7gCE5Br0PnZ6WeK4u-T5QeOvn1N52BMeJQ8aJQJ8Hh3HiQXb4_P5-_S1cfFcn60SnWekyElBaEVJ4xpoXSja6hoWRQ5hYo3oiYs41Q1FeMArNSaC1JkoOqyAciJxrhmB8mbrW4_Vh3UGuzglZG9bzvlr6VTrfz9xbYbuXZXkrECM5xHgZc7Ae--jBAG2bVBRwvRpRuDJJxjVpQ4L_-PYkpppDGL6LM_0Es3ehsnIRlhmFNOxUS92lLauxA8NLd9EyynHEiwcsqBnHIQ8ae_er2Ffy4-As93gApamSZuSrfhjuOYCPFD6MWWc2P_r5LpriTbkmBrp31rofcQwp2bvzb6HSDb2CU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3130626273</pqid></control><display><type>article</type><title>Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Complete</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Lin, Yi ; Sun, Zhongjie</creator><creatorcontrib>Lin, Yi ; Sun, Zhongjie</creatorcontrib><description>Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2012-1091</identifier><identifier>PMID: 22597535</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Aging ; Animals ; Beta cells ; Biological and medical sciences ; Calcium ; Calcium (intracellular) ; Calcium - metabolism ; Calcium Channels - metabolism ; Cell Membrane - metabolism ; Cytosol - metabolism ; Diabetes-Insulin-Glucagon-Gastrointestinal ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Glucose ; Glucose - metabolism ; Glucuronidase - metabolism ; Insulin ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - cytology ; Insulinoma ; Islets of Langerhans - cytology ; Klotho protein ; Membranes ; Mice ; Plasma ; RNA, Small Interfering - metabolism ; siRNA ; Transient receptor potential proteins ; TRPV Cation Channels - metabolism ; Up-Regulation ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2012-07, Vol.153 (7), p.3029-3039</ispartof><rights>Copyright © 2012 by The Endocrine Society</rights><rights>Copyright © 2012 by The Endocrine Society 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-1812b6133c7acfcdeb298852eb6f7d13462afb36ee39cc67184ead9fee51c00d3</citedby><cites>FETCH-LOGICAL-c551t-1812b6133c7acfcdeb298852eb6f7d13462afb36ee39cc67184ead9fee51c00d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26017791$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22597535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Yi</creatorcontrib><creatorcontrib>Sun, Zhongjie</creatorcontrib><title>Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells.</description><subject>Aging</subject><subject>Animals</subject><subject>Beta cells</subject><subject>Biological and medical sciences</subject><subject>Calcium</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Cytosol - metabolism</subject><subject>Diabetes-Insulin-Glucagon-Gastrointestinal</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucuronidase - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - cytology</subject><subject>Insulinoma</subject><subject>Islets of Langerhans - cytology</subject><subject>Klotho protein</subject><subject>Membranes</subject><subject>Mice</subject><subject>Plasma</subject><subject>RNA, Small Interfering - metabolism</subject><subject>siRNA</subject><subject>Transient receptor potential proteins</subject><subject>TRPV Cation Channels - metabolism</subject><subject>Up-Regulation</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEotPCjjWyhBAsSPFPYicbpGpUhhFTqErL1nKcm5lUjh3spFK3fSQehGfCYYYWEIiVZfnzuffce5LkCcGHhBL8GuwhxYSmBJfkXjIjZZanggh8P5lhTFgqKBV7yX4Il_GaZRl7mOxRmpciZ_ksuTmyQ6vWrV2jBVhA740bNg4d242yGgJamFG7AOnS1qOGGi1tGE1r0SfQHobWWVRdo4s-PYP1aNQw6ZwaFTqFTqCrvIqSK7gCE5Br0PnZ6WeK4u-T5QeOvn1N52BMeJQ8aJQJ8Hh3HiQXb4_P5-_S1cfFcn60SnWekyElBaEVJ4xpoXSja6hoWRQ5hYo3oiYs41Q1FeMArNSaC1JkoOqyAciJxrhmB8mbrW4_Vh3UGuzglZG9bzvlr6VTrfz9xbYbuXZXkrECM5xHgZc7Ae--jBAG2bVBRwvRpRuDJJxjVpQ4L_-PYkpppDGL6LM_0Es3ehsnIRlhmFNOxUS92lLauxA8NLd9EyynHEiwcsqBnHIQ8ae_er2Ffy4-As93gApamSZuSrfhjuOYCPFD6MWWc2P_r5LpriTbkmBrp31rofcQwp2bvzb6HSDb2CU</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Lin, Yi</creator><creator>Sun, Zhongjie</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120701</creationdate><title>Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells</title><author>Lin, Yi ; Sun, Zhongjie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-1812b6133c7acfcdeb298852eb6f7d13462afb36ee39cc67184ead9fee51c00d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Beta cells</topic><topic>Biological and medical sciences</topic><topic>Calcium</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels - metabolism</topic><topic>Cell Membrane - metabolism</topic><topic>Cytosol - metabolism</topic><topic>Diabetes-Insulin-Glucagon-Gastrointestinal</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucuronidase - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - cytology</topic><topic>Insulinoma</topic><topic>Islets of Langerhans - cytology</topic><topic>Klotho protein</topic><topic>Membranes</topic><topic>Mice</topic><topic>Plasma</topic><topic>RNA, Small Interfering - metabolism</topic><topic>siRNA</topic><topic>Transient receptor potential proteins</topic><topic>TRPV Cation Channels - metabolism</topic><topic>Up-Regulation</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Yi</creatorcontrib><creatorcontrib>Sun, Zhongjie</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Yi</au><au>Sun, Zhongjie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>153</volume><issue>7</issue><spage>3029</spage><epage>3039</epage><pages>3029-3039</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Klotho is a recently discovered antiaging gene. Klotho is expressed in mouse pancreatic islets and in insulinoma β-cells (MIN6 β-cells). The purpose of this study was to investigate whether Klotho plays a role in the regulation of insulin secretion in MIN6 β-cells by overexpression and silencing of Klotho. It is interesting that overexpression of Klotho increased glucose-induced insulin secretion in MIN6 β-cells. Overexpression of mouse Klotho protein also significantly increased plasma membrane levels of transient receptor potential V2 (TRPV2), calcium entry, and the glucose-induced increase in intracellular calcium. On the other hand, knockdown of Klotho by siRNA significantly decreased plasma membrane levels of TRPV2 and attenuated glucose-induced calcium entry and insulin secretion. Tranilast, a selective inhibitor of TRPV2, abolished the promoting effects of overexpression of Klotho on glucose-induced calcium entry and insulin secretion in MIN6 cells. Thus, TRPV2 lies in the downstream of Klotho in the regulation of glucose-induced insulin secretion. This study demonstrated, for the first time, that Klotho may enhance glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 and thus glucose-induced calcium responses. These findings reveal a previously unidentified role of Klotho in the regulation of glucose-induced insulin secretion in MIN6 β-cells.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>22597535</pmid><doi>10.1210/en.2012-1091</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Endocrinology (Philadelphia), 2012-07, Vol.153 (7), p.3029-3039 |
| issn | 0013-7227 1945-7170 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Aging Animals Beta cells Biological and medical sciences Calcium Calcium (intracellular) Calcium - metabolism Calcium Channels - metabolism Cell Membrane - metabolism Cytosol - metabolism Diabetes-Insulin-Glucagon-Gastrointestinal Fundamental and applied biological sciences. Psychology Gene Expression Regulation Glucose Glucose - metabolism Glucuronidase - metabolism Insulin Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - cytology Insulinoma Islets of Langerhans - cytology Klotho protein Membranes Mice Plasma RNA, Small Interfering - metabolism siRNA Transient receptor potential proteins TRPV Cation Channels - metabolism Up-Regulation Vertebrates: endocrinology |
| title | Antiaging Gene Klotho Enhances Glucose-Induced Insulin Secretion by Up-Regulating Plasma Membrane Levels of TRPV2 in MIN6 β-Cells |
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