Characterisation of the biological activity of xenin-25 degradation fragment peptides
Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin...
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| Veröffentlicht in: | Journal of endocrinology 2014-05, Vol.221 (2), p.193-200 |
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| creator | Martin, Christine M A Parthsarathy, Vadivel Pathak, Varun Gault, Victor A Flatt, Peter R Irwin, Nigel |
| description | Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P |
| doi_str_mv | 10.1530/JOE-13-0617 |
| format | Article |
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However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18–25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (d-Ala2)GIP. In contrast, xenin 9–25, xenin 11–25 and xenin 14–25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9–25, xenin 11–25 and xenin 14–25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10−6 M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (d-Ala2)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (d-Ala2)GIP alone. Xenin-25 and xenin 18–25 also imparted a potential synergistic effect on (d-Ala2)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18–25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.]]></description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1530/JOE-13-0617</identifier><identifier>PMID: 24520141</identifier><language>eng</language><publisher>England: Bioscientifica Ltd</publisher><subject>Animals ; Cells, Cultured ; Diet, High-Fat ; Drug Evaluation, Preclinical ; Hypoglycemic Agents - chemistry ; Hypoglycemic Agents - metabolism ; Hypoglycemic Agents - pharmacology ; Insulin - metabolism ; Insulin Secretion ; Male ; Mice ; Neurotensin - chemistry ; Neurotensin - metabolism ; Neurotensin - pharmacology ; Peptide Fragments - metabolism ; Peptide Fragments - pharmacology ; Proteolysis ; Satiation - drug effects</subject><ispartof>Journal of endocrinology, 2014-05, Vol.221 (2), p.193-200</ispartof><rights>2014 Society for Endocrinology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b368t-e3a7cbbaa49f1033a0155da9cad48b52cb506d20a5c4af1f1f530e0296e7b273</citedby><cites>FETCH-LOGICAL-b368t-e3a7cbbaa49f1033a0155da9cad48b52cb506d20a5c4af1f1f530e0296e7b273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24520141$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martin, Christine M A</creatorcontrib><creatorcontrib>Parthsarathy, Vadivel</creatorcontrib><creatorcontrib>Pathak, Varun</creatorcontrib><creatorcontrib>Gault, Victor A</creatorcontrib><creatorcontrib>Flatt, Peter R</creatorcontrib><creatorcontrib>Irwin, Nigel</creatorcontrib><title>Characterisation of the biological activity of xenin-25 degradation fragment peptides</title><title>Journal of endocrinology</title><addtitle>J Endocrinol</addtitle><description><![CDATA[Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18–25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (d-Ala2)GIP. In contrast, xenin 9–25, xenin 11–25 and xenin 14–25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9–25, xenin 11–25 and xenin 14–25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10−6 M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (d-Ala2)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (d-Ala2)GIP alone. Xenin-25 and xenin 18–25 also imparted a potential synergistic effect on (d-Ala2)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18–25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.]]></description><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Diet, High-Fat</subject><subject>Drug Evaluation, Preclinical</subject><subject>Hypoglycemic Agents - chemistry</subject><subject>Hypoglycemic Agents - metabolism</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Male</subject><subject>Mice</subject><subject>Neurotensin - chemistry</subject><subject>Neurotensin - metabolism</subject><subject>Neurotensin - pharmacology</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptide Fragments - pharmacology</subject><subject>Proteolysis</subject><subject>Satiation - drug effects</subject><issn>0022-0795</issn><issn>1479-6805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kDtPwzAURi0EoqUwsaOMSChwbcd5jKgqL1XqUubo2nFao7ywXUT_Pa5SGNEdPNzjT_c7hFxTuKeCw8PbahFTHkNKsxMypUlWxGkO4pRMARiLISvEhFw49wFABc34OZmwRDCgCZ2S9_kWLSqvrXHoTd9FfR35rY6k6Zt-YxQ2UVibL-P3h9W37kwXMxFVemOxGr_UFjet7nw06MGbSrtLclZj4_TV8Z2R9dNiPX-Jl6vn1_njMpY8zX2sOWZKSsSkqClwjuFAUWGhsEpyKZiSAtKKAQqVYE3DhL4aWJHqTLKMz8jtGDvY_nOnnS9b45RuGux0v3NlqJvnNAFIA3o3osr2zlldl4M1Ldp9SaE8aCyDxpLy8qAx0DfH4J1sdfXH_noLAB2BoMkpE7qbOrj6N_QHckV97Q</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Martin, Christine M A</creator><creator>Parthsarathy, Vadivel</creator><creator>Pathak, Varun</creator><creator>Gault, Victor A</creator><creator>Flatt, Peter R</creator><creator>Irwin, Nigel</creator><general>Bioscientifica Ltd</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>7X8</scope></search><sort><creationdate>20140501</creationdate><title>Characterisation of the biological activity of xenin-25 degradation fragment peptides</title><author>Martin, Christine M A ; Parthsarathy, Vadivel ; Pathak, Varun ; Gault, Victor A ; Flatt, Peter R ; Irwin, Nigel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b368t-e3a7cbbaa49f1033a0155da9cad48b52cb506d20a5c4af1f1f530e0296e7b273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Diet, High-Fat</topic><topic>Drug Evaluation, Preclinical</topic><topic>Hypoglycemic Agents - chemistry</topic><topic>Hypoglycemic Agents - metabolism</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Male</topic><topic>Mice</topic><topic>Neurotensin - chemistry</topic><topic>Neurotensin - metabolism</topic><topic>Neurotensin - pharmacology</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptide Fragments - pharmacology</topic><topic>Proteolysis</topic><topic>Satiation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martin, Christine M A</creatorcontrib><creatorcontrib>Parthsarathy, Vadivel</creatorcontrib><creatorcontrib>Pathak, Varun</creatorcontrib><creatorcontrib>Gault, Victor A</creatorcontrib><creatorcontrib>Flatt, Peter R</creatorcontrib><creatorcontrib>Irwin, Nigel</creatorcontrib><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>Journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martin, Christine M A</au><au>Parthsarathy, Vadivel</au><au>Pathak, Varun</au><au>Gault, Victor A</au><au>Flatt, Peter R</au><au>Irwin, Nigel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterisation of the biological activity of xenin-25 degradation fragment peptides</atitle><jtitle>Journal of endocrinology</jtitle><addtitle>J Endocrinol</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>221</volume><issue>2</issue><spage>193</spage><epage>200</epage><pages>193-200</pages><issn>0022-0795</issn><eissn>1479-6805</eissn><abstract><![CDATA[Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18–25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (d-Ala2)GIP. In contrast, xenin 9–25, xenin 11–25 and xenin 14–25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9–25, xenin 11–25 and xenin 14–25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10−6 M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (d-Ala2)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (d-Ala2)GIP alone. Xenin-25 and xenin 18–25 also imparted a potential synergistic effect on (d-Ala2)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18–25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.]]></abstract><cop>England</cop><pub>Bioscientifica Ltd</pub><pmid>24520141</pmid><doi>10.1530/JOE-13-0617</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cells, Cultured Diet, High-Fat Drug Evaluation, Preclinical Hypoglycemic Agents - chemistry Hypoglycemic Agents - metabolism Hypoglycemic Agents - pharmacology Insulin - metabolism Insulin Secretion Male Mice Neurotensin - chemistry Neurotensin - metabolism Neurotensin - pharmacology Peptide Fragments - metabolism Peptide Fragments - pharmacology Proteolysis Satiation - drug effects |
| title | Characterisation of the biological activity of xenin-25 degradation fragment peptides |
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