Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy
Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4...
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| Veröffentlicht in: | Journal of molecular endocrinology 2017-07, Vol.59 (1), p.R1-R10 |
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| description | Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure- and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations. |
| doi_str_mv | 10.1530/JME-17-0005 |
| format | Article |
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The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure- and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.</description><identifier>ISSN: 0952-5041</identifier><identifier>EISSN: 1479-6813</identifier><identifier>DOI: 10.1530/JME-17-0005</identifier><identifier>PMID: 28420715</identifier><language>eng</language><publisher>England: Bioscientifica Ltd</publisher><subject>Animals ; Blood pressure ; Chemokine CXCL12 - agonists ; Chemokine CXCL12 - genetics ; Chemokine CXCL12 - metabolism ; Clinical Trials as Topic ; Diabetes ; Diabetes mellitus ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - enzymology ; Diabetic Nephropathies - genetics ; Diabetic Nephropathies - pathology ; Dipeptidyl Peptidase 4 - genetics ; Dipeptidyl Peptidase 4 - metabolism ; Dipeptidyl-peptidase IV ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; Drug Evaluation, Preclinical ; Extracellular Matrix ; Gene Expression Regulation ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptide 1 - agonists ; Glucagon-Like Peptide 1 - genetics ; Glucagon-Like Peptide 1 - metabolism ; Glucose ; Humans ; Hypoglycemic Agents - therapeutic use ; Kidneys ; Mesangial Cells - drug effects ; Mesangial Cells - enzymology ; Mesangial Cells - pathology ; Nephropathy ; Peptidase ; Podocytes - drug effects ; Podocytes - enzymology ; Podocytes - pathology ; Protective Agents - therapeutic use ; Review ; SDF-1 protein</subject><ispartof>Journal of molecular endocrinology, 2017-07, Vol.59 (1), p.R1-R10</ispartof><rights>2017 Society for Endocrinology</rights><rights>2017 Society for Endocrinology.</rights><rights>Copyright Society for Endocrinology & BioScientifica Ltd. 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The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure- and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.</description><subject>Animals</subject><subject>Blood pressure</subject><subject>Chemokine CXCL12 - agonists</subject><subject>Chemokine CXCL12 - genetics</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Clinical Trials as Topic</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic Nephropathies - drug therapy</subject><subject>Diabetic Nephropathies - enzymology</subject><subject>Diabetic Nephropathies - genetics</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Dipeptidyl Peptidase 4 - genetics</subject><subject>Dipeptidyl Peptidase 4 - metabolism</subject><subject>Dipeptidyl-peptidase IV</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>Drug Evaluation, Preclinical</subject><subject>Extracellular Matrix</subject><subject>Gene Expression Regulation</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptide 1 - agonists</subject><subject>Glucagon-Like Peptide 1 - genetics</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Glucose</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Kidneys</subject><subject>Mesangial Cells - drug effects</subject><subject>Mesangial Cells - enzymology</subject><subject>Mesangial Cells - pathology</subject><subject>Nephropathy</subject><subject>Peptidase</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - enzymology</subject><subject>Podocytes - pathology</subject><subject>Protective Agents - therapeutic use</subject><subject>Review</subject><subject>SDF-1 protein</subject><issn>0952-5041</issn><issn>1479-6813</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMo7rp68i4FL4JEM2nSpEdZ_GRFFD2HJE0xS9vUpj3svzey6sGDp3mHeXgZHoSOgVwAz8nlw-M1BoEJIXwHzYGJEhcS8l00JyWnmBMGM3QQ45oQ4CDYPppRySgRwOfo-SU0Lgt1FkMzmRR1V2Wta82gO4dNmNJa-d71o682TbYNOjrMMt-lizZu9DbrXP8-hF6P75tDtFfrJrqj77lAbzfXr8s7vHq6vV9erbBhBR1xTUtWF7SgjkpDpDC2sI6SqiwkF5JxntfScC6rynAg2uqSFdZWrIS8pNrQfIHOtr39ED4mF0fV-mhd06THwxQVSFmKgolcJvT0D7oO09Cl7xQFAMEJ5DxR51vKDiHGwdWqH3yrh40Cor5Mq2RagVBfphN98t05mdZVv-yP2gTAFjA-ROtdN_raW_1v6Sf6rYd2</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Hasan, Ahmed A</creator><creator>Hocher, Berthold</creator><general>Bioscientifica Ltd</general><general>Society for Endocrinology & 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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201707</creationdate><title>Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy</title><author>Hasan, Ahmed A ; Hocher, Berthold</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b462t-f294f6262e28b087bc6ce20d9685784553f8b558ddb510aca946ccd491392ab23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Blood pressure</topic><topic>Chemokine CXCL12 - agonists</topic><topic>Chemokine CXCL12 - genetics</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Clinical Trials as Topic</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic Nephropathies - drug therapy</topic><topic>Diabetic Nephropathies - enzymology</topic><topic>Diabetic Nephropathies - genetics</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Dipeptidyl Peptidase 4 - genetics</topic><topic>Dipeptidyl Peptidase 4 - metabolism</topic><topic>Dipeptidyl-peptidase IV</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</topic><topic>Drug Evaluation, Preclinical</topic><topic>Extracellular Matrix</topic><topic>Gene Expression Regulation</topic><topic>Glucagon</topic><topic>Glucagon-like peptide 1</topic><topic>Glucagon-Like Peptide 1 - agonists</topic><topic>Glucagon-Like Peptide 1 - genetics</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Glucose</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Kidneys</topic><topic>Mesangial Cells - drug effects</topic><topic>Mesangial Cells - enzymology</topic><topic>Mesangial Cells - pathology</topic><topic>Nephropathy</topic><topic>Peptidase</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - enzymology</topic><topic>Podocytes - pathology</topic><topic>Protective Agents - therapeutic use</topic><topic>Review</topic><topic>SDF-1 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hasan, Ahmed A</creatorcontrib><creatorcontrib>Hocher, Berthold</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hasan, Ahmed A</au><au>Hocher, Berthold</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy</atitle><jtitle>Journal of molecular endocrinology</jtitle><addtitle>J Mol Endocrinol</addtitle><date>2017-07</date><risdate>2017</risdate><volume>59</volume><issue>1</issue><spage>R1</spage><epage>R10</epage><pages>R1-R10</pages><issn>0952-5041</issn><eissn>1479-6813</eissn><abstract>Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure- and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.</abstract><cop>England</cop><pub>Bioscientifica Ltd</pub><pmid>28420715</pmid><doi>10.1530/JME-17-0005</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Society for Endocrinology Journals |
| subjects | Animals Blood pressure Chemokine CXCL12 - agonists Chemokine CXCL12 - genetics Chemokine CXCL12 - metabolism Clinical Trials as Topic Diabetes Diabetes mellitus Diabetic Nephropathies - drug therapy Diabetic Nephropathies - enzymology Diabetic Nephropathies - genetics Diabetic Nephropathies - pathology Dipeptidyl Peptidase 4 - genetics Dipeptidyl Peptidase 4 - metabolism Dipeptidyl-peptidase IV Dipeptidyl-Peptidase IV Inhibitors - therapeutic use Drug Evaluation, Preclinical Extracellular Matrix Gene Expression Regulation Glucagon Glucagon-like peptide 1 Glucagon-Like Peptide 1 - agonists Glucagon-Like Peptide 1 - genetics Glucagon-Like Peptide 1 - metabolism Glucose Humans Hypoglycemic Agents - therapeutic use Kidneys Mesangial Cells - drug effects Mesangial Cells - enzymology Mesangial Cells - pathology Nephropathy Peptidase Podocytes - drug effects Podocytes - enzymology Podocytes - pathology Protective Agents - therapeutic use Review SDF-1 protein |
| title | Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy |
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