Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: Effects of DPP-IV inhibitor vildagliptin
Effects of DPP-IV inhibitor vildagliptin on the islets blood flow, nitric oxide, and insulin in normal and diabetic Wistar rats. The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using...
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| Veröffentlicht in: | European journal of pharmaceutical sciences 2012-04, Vol.45 (5), p.546-551 |
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| creator | Akarte, Atul sureshrao Srinivasan, B.P. Gandhi, Sonia |
| description | Effects of DPP-IV inhibitor vildagliptin on the islets blood flow, nitric oxide, and insulin in normal and diabetic Wistar rats.
The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca2+ in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO−) ions and protects from cytokine-induced suppression of insulin release. |
| doi_str_mv | 10.1016/j.ejps.2011.11.016 |
| format | Article |
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The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca2+ in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO−) ions and protects from cytokine-induced suppression of insulin release.</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2011.11.016</identifier><identifier>PMID: 22155545</identifier><language>eng</language><publisher>Kindlington: Elsevier B.V</publisher><subject>Adamantane - analogs & derivatives ; Adamantane - pharmacology ; Animals ; Biological and medical sciences ; Blood Glucose - drug effects ; Calcium - metabolism ; Cardiac Output - drug effects ; Cytokines - metabolism ; Cytosol - drug effects ; Cytosol - metabolism ; Cytosolic calcium ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetic rats ; Dipeptidyl-Peptidase IV Inhibitors - pharmacology ; General pharmacology ; Glucose - metabolism ; Hemodynamics - drug effects ; Insulin ; Insulin - blood ; Insulin - metabolism ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Islets blood flow ; Medical sciences ; Nitric oxide ; Nitric Oxide - metabolism ; Nitriles - pharmacology ; Peroxynitrous Acid - metabolism ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Pyrrolidines - pharmacology ; Rats ; Rats, Wistar ; Regional Blood Flow - drug effects ; Vildagliptin</subject><ispartof>European journal of pharmaceutical sciences, 2012-04, Vol.45 (5), p.546-551</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-e81abe9bd687b3f6c37b889f48e097fc6654f4dc55929b91f1929277775993113</citedby><cites>FETCH-LOGICAL-c385t-e81abe9bd687b3f6c37b889f48e097fc6654f4dc55929b91f1929277775993113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejps.2011.11.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25609432$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22155545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akarte, Atul sureshrao</creatorcontrib><creatorcontrib>Srinivasan, B.P.</creatorcontrib><creatorcontrib>Gandhi, Sonia</creatorcontrib><title>Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: Effects of DPP-IV inhibitor vildagliptin</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>Effects of DPP-IV inhibitor vildagliptin on the islets blood flow, nitric oxide, and insulin in normal and diabetic Wistar rats.
The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca2+ in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO−) ions and protects from cytokine-induced suppression of insulin release.</description><subject>Adamantane - analogs & derivatives</subject><subject>Adamantane - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - drug effects</subject><subject>Calcium - metabolism</subject><subject>Cardiac Output - drug effects</subject><subject>Cytokines - metabolism</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Cytosolic calcium</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetic rats</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - pharmacology</subject><subject>General pharmacology</subject><subject>Glucose - metabolism</subject><subject>Hemodynamics - drug effects</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Insulin - metabolism</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Islets blood flow</subject><subject>Medical sciences</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitriles - pharmacology</subject><subject>Peroxynitrous Acid - metabolism</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrrolidines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Regional Blood Flow - drug effects</subject><subject>Vildagliptin</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhiMEotvCC3BAviAum8VO4iRGXFBboFIlKgRcLccZs7Pyxqntbem78LDMahe4YY000sw3v-1_iuKF4CvBRftms4LNnFYVF2JFQaVHxUL0nSp5V_HHxYKrqi-56ruT4jSlDee87Tv-tDipKiGlbOSi-PUFvMkYprTGObEB8j3AxPIaGCYPmUo-hJE5H-6XbMIc0bLwE0dYMpzSzuO0ZGYamX3IIQVPXWu8xd2W2iyazGYz2Qh0hz0qvmWXzoEl6eDYxc1NefWd2DUOmENkd-hH88PjnHF6Vjxxxid4fsxnxbcPl1_PP5XXnz9enb-_Lm3dy1xCL8wAahjpd0PtWlt3Q98r1_TAVeds28rGNaOVUlVqUMIJylVHRypVC1GfFa8PunMMtztIWW8xWfDeTBB2SauqlbzhoiGyOpA2hpQiOD1H3Jr4oAXX-6Xojd4vRe-XoimoREMvj_K7YQvj35E_WyDg1REwidxzkSzD9I-TLVdNXRH37sABmXGHEHWyCJOFESMZqseA_3vHb2VOrHI</recordid><startdate>20120411</startdate><enddate>20120411</enddate><creator>Akarte, Atul sureshrao</creator><creator>Srinivasan, B.P.</creator><creator>Gandhi, Sonia</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20120411</creationdate><title>Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: Effects of DPP-IV inhibitor vildagliptin</title><author>Akarte, Atul sureshrao ; Srinivasan, B.P. ; Gandhi, Sonia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-e81abe9bd687b3f6c37b889f48e097fc6654f4dc55929b91f1929277775993113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adamantane - analogs & derivatives</topic><topic>Adamantane - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - drug effects</topic><topic>Calcium - metabolism</topic><topic>Cardiac Output - drug effects</topic><topic>Cytokines - metabolism</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Cytosolic calcium</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetic rats</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - pharmacology</topic><topic>General pharmacology</topic><topic>Glucose - metabolism</topic><topic>Hemodynamics - drug effects</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin - metabolism</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Islets blood flow</topic><topic>Medical sciences</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitriles - pharmacology</topic><topic>Peroxynitrous Acid - metabolism</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrrolidines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Regional Blood Flow - drug effects</topic><topic>Vildagliptin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akarte, Atul sureshrao</creatorcontrib><creatorcontrib>Srinivasan, B.P.</creatorcontrib><creatorcontrib>Gandhi, Sonia</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>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akarte, Atul sureshrao</au><au>Srinivasan, B.P.</au><au>Gandhi, Sonia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: Effects of DPP-IV inhibitor vildagliptin</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2012-04-11</date><risdate>2012</risdate><volume>45</volume><issue>5</issue><spage>546</spage><epage>551</epage><pages>546-551</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>Effects of DPP-IV inhibitor vildagliptin on the islets blood flow, nitric oxide, and insulin in normal and diabetic Wistar rats.
The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. For measuring pancreatic and islets blood a non-radioactive microsphere technique was used. Vehicle pre-treatment of glucose administered diabetic rats had decrease pancreatic and islets blood flow as compared with glucose administered normal rats. Blood glucose concentrations were not affected after vildagliptin administration in either diabetic or normal rats (10min after glucose administration). Vildagliptin had no effects on baseline pancreatic or islets blood flow in glucose administered normal rats. Administration of vildagliptin increased both pancreatic and islets blood flow as compared with vehicle treated diabetic rats. Furthermore, diabetic rats showed significant increase in NO and decrease in insulin secretions and vice versa in normal rats. Vildagliptin pre-treatment to both normal and diabetic rats had shown mild decrease in NO, but significantly increased insulin secretions. In addition, vildagliptin itself is able to mobilize intracellular Ca2+ in pancreatic islets both in absence and presence of glucose. From the present study, we conclude following points (A) administration of vildagliptin augmented the blood flow seen in islets of diabetic rats, (B) islets insulin secretions are independent of islets blood flow and NO, (C) vildagliptin inhibited excessive NO production in diabetic rats that prevents the damage to β-cells due to excessive production of peroxynitrite (ONOO−) ions and protects from cytokine-induced suppression of insulin release.</abstract><cop>Kindlington</cop><pub>Elsevier B.V</pub><pmid>22155545</pmid><doi>10.1016/j.ejps.2011.11.016</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | European journal of pharmaceutical sciences, 2012-04, Vol.45 (5), p.546-551 |
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| subjects | Adamantane - analogs & derivatives Adamantane - pharmacology Animals Biological and medical sciences Blood Glucose - drug effects Calcium - metabolism Cardiac Output - drug effects Cytokines - metabolism Cytosol - drug effects Cytosol - metabolism Cytosolic calcium Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetic rats Dipeptidyl-Peptidase IV Inhibitors - pharmacology General pharmacology Glucose - metabolism Hemodynamics - drug effects Insulin Insulin - blood Insulin - metabolism Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Islets blood flow Medical sciences Nitric oxide Nitric Oxide - metabolism Nitriles - pharmacology Peroxynitrous Acid - metabolism Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Pyrrolidines - pharmacology Rats Rats, Wistar Regional Blood Flow - drug effects Vildagliptin |
| title | Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: Effects of DPP-IV inhibitor vildagliptin |
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