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Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion
•DPP-4 activity is increased in hyperglycaemia and insulin resistance.•Enzyme activity, protein and gene expression of DPP-4 are up-regulated in high fat diet-induced obesity in mice.•Tissue distribution patterns of DPP-4 demonstrate highest levels in the small intestine and lungs.•Treatment of HFF...
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| Published in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2018-02, Vol.100, p.165-172 |
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| container_title | Peptides (New York, N.Y. : 1980) |
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| creator | McKillop, Aine M. Stevenson, Claire L. Moran, Brian M. Abdel-Wahab, Yasser H.A. Flatt, Peter R. |
| description | •DPP-4 activity is increased in hyperglycaemia and insulin resistance.•Enzyme activity, protein and gene expression of DPP-4 are up-regulated in high fat diet-induced obesity in mice.•Tissue distribution patterns of DPP-4 demonstrate highest levels in the small intestine and lungs.•Treatment of HFF mice with metformin inhibits DPP-4 activity which may modulate incretin action and control hyperglycaemia.
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p |
| doi_str_mv | 10.1016/j.peptides.2017.12.020 |
| format | article |
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Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < .01). Tissue distribution patterns in lean and HFF mice demonstrated highest levels of DPP-4 activity in lung (20–26 μmol/min/mg protein) and small intestine (13–14 μmol/min/mg protein), and lowest activity in the spleen (3.8 μmol/min/mg protein). Modulation of DPP-4 activity by high fat feeding was observed in several tissues with increases in the lung (p < .05), liver (p < .05), kidney (p < .05) and pancreas (p < .05). With a high fat diet, DPP-4 gene expression was upregulated in the liver (p < .001) and downregulated in the pancreas (p < 0.001) and small intestine (p < .001). Immunohistochemical analysis revealed increased DPP-4 immunostaining localised primarily in the pancreatic islets of HFF mice (p < .01) with no change in islet GLP-1 expression. Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p < .05), decreased blood glucose (p < .05) and increased GLP-1 gene expression (p < .001). These data indicate that DPP-4 is modulated in a tissue specific manner and is dependent on physiological conditions such as hyperglycaemia and insulin resistance, suggesting a significant role in disorders such as diabetes.]]></description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2017.12.020</identifier><identifier>PMID: 29412816</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blood Glucose - drug effects ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Diet, High-Fat - adverse effects ; Dipeptidyl Peptidase 4 - genetics ; Dipeptidyl Peptidase 4 - metabolism ; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage ; Dipeptidyl-peptidase-4 (DPP-4) ; Gene Expression Regulation - drug effects ; Glucagon-Like Peptide 1 - genetics ; Glucagon-Like Peptide 1 - metabolism ; Glucose - metabolism ; High fat fed ; Humans ; Hypoglycemic Agents - administration & dosage ; Insulin - genetics ; Insulin - metabolism ; Insulin resistance ; Insulin Resistance - genetics ; Insulin Secretion - drug effects ; Islet ; Islets of Langerhans - drug effects ; Islets of Langerhans - pathology ; Metformin - administration & dosage ; Mice ; Obesity - drug therapy ; Obesity - etiology ; Obesity - metabolism ; Obesity - pathology ; Type 2 diabetes</subject><ispartof>Peptides (New York, N.Y. : 1980), 2018-02, Vol.100, p.165-172</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-97d9fc79c87823a3620edf57b625626bbf4c668e9eef06dab5fb84e6ddd7d6ad3</citedby><cites>FETCH-LOGICAL-c434t-97d9fc79c87823a3620edf57b625626bbf4c668e9eef06dab5fb84e6ddd7d6ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29412816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McKillop, Aine M.</creatorcontrib><creatorcontrib>Stevenson, Claire L.</creatorcontrib><creatorcontrib>Moran, Brian M.</creatorcontrib><creatorcontrib>Abdel-Wahab, Yasser H.A.</creatorcontrib><creatorcontrib>Flatt, Peter R.</creatorcontrib><title>Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description><![CDATA[•DPP-4 activity is increased in hyperglycaemia and insulin resistance.•Enzyme activity, protein and gene expression of DPP-4 are up-regulated in high fat diet-induced obesity in mice.•Tissue distribution patterns of DPP-4 demonstrate highest levels in the small intestine and lungs.•Treatment of HFF mice with metformin inhibits DPP-4 activity which may modulate incretin action and control hyperglycaemia.
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < .01). Tissue distribution patterns in lean and HFF mice demonstrated highest levels of DPP-4 activity in lung (20–26 μmol/min/mg protein) and small intestine (13–14 μmol/min/mg protein), and lowest activity in the spleen (3.8 μmol/min/mg protein). Modulation of DPP-4 activity by high fat feeding was observed in several tissues with increases in the lung (p < .05), liver (p < .05), kidney (p < .05) and pancreas (p < .05). With a high fat diet, DPP-4 gene expression was upregulated in the liver (p < .001) and downregulated in the pancreas (p < 0.001) and small intestine (p < .001). Immunohistochemical analysis revealed increased DPP-4 immunostaining localised primarily in the pancreatic islets of HFF mice (p < .01) with no change in islet GLP-1 expression. Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p < .05), decreased blood glucose (p < .05) and increased GLP-1 gene expression (p < .001). These data indicate that DPP-4 is modulated in a tissue specific manner and is dependent on physiological conditions such as hyperglycaemia and insulin resistance, suggesting a significant role in disorders such as diabetes.]]></description><subject>Animals</subject><subject>Blood Glucose - drug effects</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Dipeptidyl Peptidase 4 - genetics</subject><subject>Dipeptidyl Peptidase 4 - metabolism</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - administration & dosage</subject><subject>Dipeptidyl-peptidase-4 (DPP-4)</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucagon-Like Peptide 1 - genetics</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Glucose - metabolism</subject><subject>High fat fed</subject><subject>Humans</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Insulin - genetics</subject><subject>Insulin - metabolism</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - genetics</subject><subject>Insulin Secretion - drug effects</subject><subject>Islet</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - pathology</subject><subject>Metformin - administration & dosage</subject><subject>Mice</subject><subject>Obesity - drug therapy</subject><subject>Obesity - etiology</subject><subject>Obesity - metabolism</subject><subject>Obesity - pathology</subject><subject>Type 2 diabetes</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkE9P3DAQxa0KVJalXwH52EuC7WTt-NaKPy0SUjkAV8uxx5VX2SR4kor99jjahWtP1njeezPzI-SSs5IzLq-25QjjFD1gKRhXJRclE-wLWfFGVcWGS31CVoxrWWjV8DNyjrhljNW1br6SM6FrLhouV-T1KSLOQOFtTIAYh54Ogd48Phb3LzTmogWM077w0bYwAVLbe7ob_NzZaUh7CiGAm5Bm33EhmuDv0j1GxR7nLgchuATL5wU5DbZD-HZ81-T57vbp-nfx8OfX_fXPh8LVVT3ltb0OTmnXqEZUtpKCgQ8b1UqxkUK2baidlA1ogMCkt-0mtE0N0nuvvLS-WpPvh9wxDa8z4GR2ER10ne1hmNFwrbVUauG1JvIgdWlATBDMmOLOpr3hzCy4zdZ84DYLbsOFybiz8fI4Y2534D9tH3yz4MdBAPnSfxGSQRehd-BjytyMH-L_ZrwDvTmXkg</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>McKillop, Aine M.</creator><creator>Stevenson, Claire L.</creator><creator>Moran, Brian M.</creator><creator>Abdel-Wahab, Yasser H.A.</creator><creator>Flatt, Peter R.</creator><general>Elsevier Inc</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>201802</creationdate><title>Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion</title><author>McKillop, Aine M. ; Stevenson, Claire L. ; Moran, Brian M. ; Abdel-Wahab, Yasser H.A. ; Flatt, Peter R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-97d9fc79c87823a3620edf57b625626bbf4c668e9eef06dab5fb84e6ddd7d6ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Blood Glucose - drug effects</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Dipeptidyl Peptidase 4 - genetics</topic><topic>Dipeptidyl Peptidase 4 - metabolism</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - administration & dosage</topic><topic>Dipeptidyl-peptidase-4 (DPP-4)</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucagon-Like Peptide 1 - genetics</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Glucose - metabolism</topic><topic>High fat fed</topic><topic>Humans</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Insulin - genetics</topic><topic>Insulin - metabolism</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - genetics</topic><topic>Insulin Secretion - drug effects</topic><topic>Islet</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - pathology</topic><topic>Metformin - administration & dosage</topic><topic>Mice</topic><topic>Obesity - drug therapy</topic><topic>Obesity - etiology</topic><topic>Obesity - metabolism</topic><topic>Obesity - pathology</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McKillop, Aine M.</creatorcontrib><creatorcontrib>Stevenson, Claire L.</creatorcontrib><creatorcontrib>Moran, Brian M.</creatorcontrib><creatorcontrib>Abdel-Wahab, Yasser H.A.</creatorcontrib><creatorcontrib>Flatt, Peter R.</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>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McKillop, Aine M.</au><au>Stevenson, Claire L.</au><au>Moran, Brian M.</au><au>Abdel-Wahab, Yasser H.A.</au><au>Flatt, Peter R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2018-02</date><risdate>2018</risdate><volume>100</volume><spage>165</spage><epage>172</epage><pages>165-172</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract><![CDATA[•DPP-4 activity is increased in hyperglycaemia and insulin resistance.•Enzyme activity, protein and gene expression of DPP-4 are up-regulated in high fat diet-induced obesity in mice.•Tissue distribution patterns of DPP-4 demonstrate highest levels in the small intestine and lungs.•Treatment of HFF mice with metformin inhibits DPP-4 activity which may modulate incretin action and control hyperglycaemia.
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < .01). Tissue distribution patterns in lean and HFF mice demonstrated highest levels of DPP-4 activity in lung (20–26 μmol/min/mg protein) and small intestine (13–14 μmol/min/mg protein), and lowest activity in the spleen (3.8 μmol/min/mg protein). Modulation of DPP-4 activity by high fat feeding was observed in several tissues with increases in the lung (p < .05), liver (p < .05), kidney (p < .05) and pancreas (p < .05). With a high fat diet, DPP-4 gene expression was upregulated in the liver (p < .001) and downregulated in the pancreas (p < 0.001) and small intestine (p < .001). Immunohistochemical analysis revealed increased DPP-4 immunostaining localised primarily in the pancreatic islets of HFF mice (p < .01) with no change in islet GLP-1 expression. Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p < .05), decreased blood glucose (p < .05) and increased GLP-1 gene expression (p < .001). These data indicate that DPP-4 is modulated in a tissue specific manner and is dependent on physiological conditions such as hyperglycaemia and insulin resistance, suggesting a significant role in disorders such as diabetes.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29412816</pmid><doi>10.1016/j.peptides.2017.12.020</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0196-9781 |
| ispartof | Peptides (New York, N.Y. : 1980), 2018-02, Vol.100, p.165-172 |
| issn | 0196-9781 1873-5169 |
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| source | ScienceDirect Freedom Collection |
| subjects | Animals Blood Glucose - drug effects Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology Diet, High-Fat - adverse effects Dipeptidyl Peptidase 4 - genetics Dipeptidyl Peptidase 4 - metabolism Dipeptidyl-Peptidase IV Inhibitors - administration & dosage Dipeptidyl-peptidase-4 (DPP-4) Gene Expression Regulation - drug effects Glucagon-Like Peptide 1 - genetics Glucagon-Like Peptide 1 - metabolism Glucose - metabolism High fat fed Humans Hypoglycemic Agents - administration & dosage Insulin - genetics Insulin - metabolism Insulin resistance Insulin Resistance - genetics Insulin Secretion - drug effects Islet Islets of Langerhans - drug effects Islets of Langerhans - pathology Metformin - administration & dosage Mice Obesity - drug therapy Obesity - etiology Obesity - metabolism Obesity - pathology Type 2 diabetes |
| title | Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion |
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