Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets
The scarcity of human cadaveric pancreata limits large‐scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen‐free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in in...
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| Veröffentlicht in: | Xenotransplantation (Københaven) 2014-07, Vol.21 (4), p.385-391 |
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| creator | Kelly, Amy C. Steyn, Leah V. Kitzmann, Jenna P. Anderson, Miranda J. Mueller, Kate R. Hart, Nathaniel J. Lynch, Ronald M. Papas, Klearchos K. Limesand, Sean W. |
| description | The scarcity of human cadaveric pancreata limits large‐scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen‐free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon‐like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti‐diabetic sulfonylurea, and exendin‐4, a GLP‐1 mimetic, potentiated glucose‐stimulated insulin secretion >2‐fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P |
| doi_str_mv | 10.1111/xen.12101 |
| format | Article |
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Islets isolated from pathogen‐free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon‐like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti‐diabetic sulfonylurea, and exendin‐4, a GLP‐1 mimetic, potentiated glucose‐stimulated insulin secretion >2‐fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P < 0.05) and had a half maximal inhibitory concentration of 60 nm in porcine islets (95% confidence interval of 45–830 nm). The epinephrine action was inhibited by the ADRα2A antagonist yohimbine. Our findings demonstrate that porcine islets express and are responsive to both stimulatory and inhibitory membrane localized receptors, which can be used as imaging targets after transplantation or to modify insulin secretion.</description><identifier>ISSN: 0908-665X</identifier><identifier>EISSN: 1399-3089</identifier><identifier>DOI: 10.1111/xen.12101</identifier><identifier>PMID: 24801676</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Animals ; epinephrine ; Epinephrine - pharmacology ; exendin-4 ; glibenclamide ; Glucagon-Like Peptide-1 Receptor ; Glyburide - pharmacology ; Humans ; Insulin - metabolism ; Insulin Secretion ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Islets of Langerhans Transplantation ; porcine islet ; Potassium Channels, Inwardly Rectifying - genetics ; Potassium Channels, Inwardly Rectifying - metabolism ; Receptors, Adrenergic, alpha-2 - genetics ; Receptors, Adrenergic, alpha-2 - metabolism ; Receptors, Glucagon - genetics ; Receptors, Glucagon - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sulfonylurea Receptors - genetics ; Sulfonylurea Receptors - metabolism ; Sus scrofa - metabolism ; Transplantation, Heterologous</subject><ispartof>Xenotransplantation (Københaven), 2014-07, Vol.21 (4), p.385-391</ispartof><rights>2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3981-894b3cac9b5a0b96de9aa447aa15d47b72e5768065a7b961255c39d8f0fc3ad43</citedby><cites>FETCH-LOGICAL-c3981-894b3cac9b5a0b96de9aa447aa15d47b72e5768065a7b961255c39d8f0fc3ad43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fxen.12101$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fxen.12101$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24801676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelly, Amy C.</creatorcontrib><creatorcontrib>Steyn, Leah V.</creatorcontrib><creatorcontrib>Kitzmann, Jenna P.</creatorcontrib><creatorcontrib>Anderson, Miranda J.</creatorcontrib><creatorcontrib>Mueller, Kate R.</creatorcontrib><creatorcontrib>Hart, Nathaniel J.</creatorcontrib><creatorcontrib>Lynch, Ronald M.</creatorcontrib><creatorcontrib>Papas, Klearchos K.</creatorcontrib><creatorcontrib>Limesand, Sean W.</creatorcontrib><title>Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets</title><title>Xenotransplantation (Københaven)</title><addtitle>Xenotransplantation</addtitle><description>The scarcity of human cadaveric pancreata limits large‐scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen‐free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon‐like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti‐diabetic sulfonylurea, and exendin‐4, a GLP‐1 mimetic, potentiated glucose‐stimulated insulin secretion >2‐fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P < 0.05) and had a half maximal inhibitory concentration of 60 nm in porcine islets (95% confidence interval of 45–830 nm). The epinephrine action was inhibited by the ADRα2A antagonist yohimbine. Our findings demonstrate that porcine islets express and are responsive to both stimulatory and inhibitory membrane localized receptors, which can be used as imaging targets after transplantation or to modify insulin secretion.</description><subject>Animals</subject><subject>epinephrine</subject><subject>Epinephrine - pharmacology</subject><subject>exendin-4</subject><subject>glibenclamide</subject><subject>Glucagon-Like Peptide-1 Receptor</subject><subject>Glyburide - pharmacology</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Islets of Langerhans Transplantation</subject><subject>porcine islet</subject><subject>Potassium Channels, Inwardly Rectifying - genetics</subject><subject>Potassium Channels, Inwardly Rectifying - metabolism</subject><subject>Receptors, Adrenergic, alpha-2 - genetics</subject><subject>Receptors, Adrenergic, alpha-2 - metabolism</subject><subject>Receptors, Glucagon - genetics</subject><subject>Receptors, Glucagon - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sulfonylurea Receptors - genetics</subject><subject>Sulfonylurea Receptors - metabolism</subject><subject>Sus scrofa - metabolism</subject><subject>Transplantation, Heterologous</subject><issn>0908-665X</issn><issn>1399-3089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtv1DAUhS0EokNhwR9AXlKpae04fmSJqnZAjAoLqs7OcpybkanHDnaizvz7up22O-7mvr5zFgehz5Sc0VLnOwhntKaEvkELytq2YkS1b9GCtERVQvD1EfqQ819CCOOKv0dHdaMIFVIs0Hw1Bzu5GLAJPYbdmCDnxzUOOM9-iGHv5wTmFJs-QYC0cfb0id342ZpNDJV3d4BHGCfXA6Y4gS1zTBm7gF2O3kzQ4zEm6wKUg4cpf0TvBuMzfHrux-jm6vLPxfdq9Wv54-LbqrKsVbRSbdMxa2zbcUO6VvTQGtM00hjK-0Z2sgYuhSKCG1netOa8CHs1kMEy0zfsGH09-I4p_pshT3rrsgXvTYA4Z025aBinkqqCnhxQm2LOCQY9Jrc1aa8p0Y8p65Kyfkq5sF-ebeduC_0r-RJrAc4PwL3zsP-_k15fXr9YVgeFyxPsXhUm3WkhmeT69nqp65XgP5frpf7NHgBLwpdt</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Kelly, Amy C.</creator><creator>Steyn, Leah V.</creator><creator>Kitzmann, Jenna P.</creator><creator>Anderson, Miranda J.</creator><creator>Mueller, Kate R.</creator><creator>Hart, Nathaniel J.</creator><creator>Lynch, Ronald M.</creator><creator>Papas, Klearchos K.</creator><creator>Limesand, Sean W.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201407</creationdate><title>Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets</title><author>Kelly, Amy C. ; Steyn, Leah V. ; Kitzmann, Jenna P. ; Anderson, Miranda J. ; Mueller, Kate R. ; Hart, Nathaniel J. ; Lynch, Ronald M. ; Papas, Klearchos K. ; Limesand, Sean W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3981-894b3cac9b5a0b96de9aa447aa15d47b72e5768065a7b961255c39d8f0fc3ad43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>epinephrine</topic><topic>Epinephrine - pharmacology</topic><topic>exendin-4</topic><topic>glibenclamide</topic><topic>Glucagon-Like Peptide-1 Receptor</topic><topic>Glyburide - pharmacology</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Islets of Langerhans Transplantation</topic><topic>porcine islet</topic><topic>Potassium Channels, Inwardly Rectifying - genetics</topic><topic>Potassium Channels, Inwardly Rectifying - metabolism</topic><topic>Receptors, Adrenergic, alpha-2 - genetics</topic><topic>Receptors, Adrenergic, alpha-2 - metabolism</topic><topic>Receptors, Glucagon - genetics</topic><topic>Receptors, Glucagon - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sulfonylurea Receptors - genetics</topic><topic>Sulfonylurea Receptors - metabolism</topic><topic>Sus scrofa - metabolism</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelly, Amy C.</creatorcontrib><creatorcontrib>Steyn, Leah V.</creatorcontrib><creatorcontrib>Kitzmann, Jenna P.</creatorcontrib><creatorcontrib>Anderson, Miranda J.</creatorcontrib><creatorcontrib>Mueller, Kate R.</creatorcontrib><creatorcontrib>Hart, Nathaniel J.</creatorcontrib><creatorcontrib>Lynch, Ronald M.</creatorcontrib><creatorcontrib>Papas, Klearchos K.</creatorcontrib><creatorcontrib>Limesand, Sean W.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Xenotransplantation (Københaven)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelly, Amy C.</au><au>Steyn, Leah V.</au><au>Kitzmann, Jenna P.</au><au>Anderson, Miranda J.</au><au>Mueller, Kate R.</au><au>Hart, Nathaniel J.</au><au>Lynch, Ronald M.</au><au>Papas, Klearchos K.</au><au>Limesand, Sean W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets</atitle><jtitle>Xenotransplantation (Københaven)</jtitle><addtitle>Xenotransplantation</addtitle><date>2014-07</date><risdate>2014</risdate><volume>21</volume><issue>4</issue><spage>385</spage><epage>391</epage><pages>385-391</pages><issn>0908-665X</issn><eissn>1399-3089</eissn><abstract>The scarcity of human cadaveric pancreata limits large‐scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen‐free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon‐like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti‐diabetic sulfonylurea, and exendin‐4, a GLP‐1 mimetic, potentiated glucose‐stimulated insulin secretion >2‐fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P < 0.05) and had a half maximal inhibitory concentration of 60 nm in porcine islets (95% confidence interval of 45–830 nm). The epinephrine action was inhibited by the ADRα2A antagonist yohimbine. Our findings demonstrate that porcine islets express and are responsive to both stimulatory and inhibitory membrane localized receptors, which can be used as imaging targets after transplantation or to modify insulin secretion.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>24801676</pmid><doi>10.1111/xen.12101</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Xenotransplantation (Københaven), 2014-07, Vol.21 (4), p.385-391 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals epinephrine Epinephrine - pharmacology exendin-4 glibenclamide Glucagon-Like Peptide-1 Receptor Glyburide - pharmacology Humans Insulin - metabolism Insulin Secretion Islets of Langerhans - drug effects Islets of Langerhans - metabolism Islets of Langerhans Transplantation porcine islet Potassium Channels, Inwardly Rectifying - genetics Potassium Channels, Inwardly Rectifying - metabolism Receptors, Adrenergic, alpha-2 - genetics Receptors, Adrenergic, alpha-2 - metabolism Receptors, Glucagon - genetics Receptors, Glucagon - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Sulfonylurea Receptors - genetics Sulfonylurea Receptors - metabolism Sus scrofa - metabolism Transplantation, Heterologous |
| title | Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets |
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