The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors
A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stim...
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| description | A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor. |
| doi_str_mv | 10.1155/2014/368703 |
| format | Article |
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Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2014/368703</identifier><identifier>PMID: 25140306</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Binding sites ; Biomedical research ; Blood Glucose ; Complications and side effects ; Diabetes ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - pathology ; Dipeptidyl Peptidase 4 - biosynthesis ; Dipeptidyl Peptidase 4 - genetics ; Dipeptidyl Peptidase 4 - metabolism ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; Dosage and administration ; Fluids ; Gastric Inhibitory Polypeptide - metabolism ; Glucagon-Like Peptide 1 - metabolism ; Heart rate ; Hormones ; Humans ; Hypoglycemic agents ; Hypoglycemic Agents - therapeutic use ; Hypoxia ; Insulin ; Insulin - metabolism ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Peptides ; Pharmaceutical research ; Plasma ; Proteins ; Review ; Signal Transduction - drug effects ; Studies</subject><ispartof>BioMed research international, 2014-01, Vol.2014 (2014), p.1-10</ispartof><rights>Copyright © 2014 Na-Hyung Kim et al.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 Na-Hyung Kim et al. Na-Hyung Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Na-Hyung Kim et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-a0e11c98c444625b2e6b6603979339eb2787a563316dcacc2f625669065e52ad3</citedby><cites>FETCH-LOGICAL-c593t-a0e11c98c444625b2e6b6603979339eb2787a563316dcacc2f625669065e52ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129137/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129137/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25140306$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kang, Dae Gill</contributor><creatorcontrib>Kim, Na Hyung</creatorcontrib><creatorcontrib>Yu, Taeyang</creatorcontrib><creatorcontrib>Lee, Dae Ho</creatorcontrib><title>The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.</description><subject>Binding sites</subject><subject>Biomedical research</subject><subject>Blood Glucose</subject><subject>Complications and side effects</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Dipeptidyl Peptidase 4 - biosynthesis</subject><subject>Dipeptidyl Peptidase 4 - genetics</subject><subject>Dipeptidyl Peptidase 4 - metabolism</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>Dosage and administration</subject><subject>Fluids</subject><subject>Gastric Inhibitory Polypeptide - metabolism</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Heart rate</subject><subject>Hormones</subject><subject>Humans</subject><subject>Hypoglycemic agents</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Hypoxia</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Peptides</subject><subject>Pharmaceutical research</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Review</subject><subject>Signal Transduction - drug effects</subject><subject>Studies</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqN0Utv1DAUBWALgWhVumINisQGgUJ9_bhOJIQ0Kq9KFbAoa8txbmZcZeJpnAHNv8fTlOGxAW9iKZ-O7XsYewz8FYDWZ4KDOpNYGS7vsWMhQZUICu4f9lIesdOUrnleFSCv8SE7EhoUlxyP2eurFRWf4rDsd57WwRcLP4U4pCJ2xduwoc0U2l1ffLnduESlKi6GVWjCFMf0iD3oXJ_o9O57wr6-f3d1_rG8_Pzh4nxxWXpdy6l0nAB8XXmlFArdCMIGkcva1FLW1AhTGadRSsDWO-9FlxVizVGTFq6VJ-zNnLvZNmtqPQ3T6Hq7GcPajTsbXbB__hnCyi7jN6tA1CBNDnh-FzDGmy2lya5D8tT3bqC4TRYQ8mxAm_-gGg3XeZY602d_0eu4HYc8iay0qFR-ofqllq4nG4Yu5iv6fahdKGG4EOb22Jez8mNMaaTu8Drgdt-03Tdt56azfvr7QA72Z68ZvJjBKgyt-x7-kfZkxpQJde6AFaLKFf0AsAe1iQ</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Kim, Na Hyung</creator><creator>Yu, Taeyang</creator><creator>Lee, Dae Ho</creator><general>Hindawi Puplishing Corporation</general><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140101</creationdate><title>The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors</title><author>Kim, Na Hyung ; Yu, Taeyang ; Lee, Dae Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-a0e11c98c444625b2e6b6603979339eb2787a563316dcacc2f625669065e52ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Binding sites</topic><topic>Biomedical research</topic><topic>Blood Glucose</topic><topic>Complications and side effects</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Dipeptidyl Peptidase 4 - biosynthesis</topic><topic>Dipeptidyl Peptidase 4 - genetics</topic><topic>Dipeptidyl Peptidase 4 - metabolism</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</topic><topic>Dosage and administration</topic><topic>Fluids</topic><topic>Gastric Inhibitory Polypeptide - metabolism</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Heart rate</topic><topic>Hormones</topic><topic>Humans</topic><topic>Hypoglycemic agents</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Hypoxia</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Peptides</topic><topic>Pharmaceutical research</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Review</topic><topic>Signal Transduction - drug effects</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Na Hyung</creatorcontrib><creatorcontrib>Yu, Taeyang</creatorcontrib><creatorcontrib>Lee, Dae Ho</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Na Hyung</au><au>Yu, Taeyang</au><au>Lee, Dae Ho</au><au>Kang, Dae Gill</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>2014</volume><issue>2014</issue><spage>1</spage><epage>10</epage><pages>1-10</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>25140306</pmid><doi>10.1155/2014/368703</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Binding sites Biomedical research Blood Glucose Complications and side effects Diabetes Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - pathology Dipeptidyl Peptidase 4 - biosynthesis Dipeptidyl Peptidase 4 - genetics Dipeptidyl Peptidase 4 - metabolism Dipeptidyl-Peptidase IV Inhibitors - therapeutic use Dosage and administration Fluids Gastric Inhibitory Polypeptide - metabolism Glucagon-Like Peptide 1 - metabolism Heart rate Hormones Humans Hypoglycemic agents Hypoglycemic Agents - therapeutic use Hypoxia Insulin Insulin - metabolism Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism Peptides Pharmaceutical research Plasma Proteins Review Signal Transduction - drug effects Studies |
| title | The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors |
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