Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents
Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the whit...
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| Veröffentlicht in: | Diabetologia 2006-02, Vol.49 (2), p.387-393 |
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| creator | Somm, E Cettour-Rose, P Asensio, C Charollais, A Klein, M Theander-Carrillo, C Juge-Aubry, C. E Dayer, J. -M Nicklin, M. J. H Meda, P Rohner-Jeanrenaud, F Meier, C. A |
| description | Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn -/- animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn -/- animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance. |
| doi_str_mv | 10.1007/s00125-005-0046-x |
| format | Article |
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E ; Dayer, J. -M ; Nicklin, M. J. H ; Meda, P ; Rohner-Jeanrenaud, F ; Meier, C. A</creator><creatorcontrib>Somm, E ; Cettour-Rose, P ; Asensio, C ; Charollais, A ; Klein, M ; Theander-Carrillo, C ; Juge-Aubry, C. E ; Dayer, J. -M ; Nicklin, M. J. H ; Meda, P ; Rohner-Jeanrenaud, F ; Meier, C. A</creatorcontrib><description>Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn -/- animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn -/- animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-005-0046-x</identifier><identifier>PMID: 16385385</identifier><language>eng</language><publisher>Berlin: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adipose Tissue - physiopathology ; Animals ; Biological and medical sciences ; Blood Glucose - analysis ; Body fat ; Cytokines ; Diabetes. Impaired glucose tolerance ; Diet ; Dietary Fats - adverse effects ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Gene Deletion ; Gene Expression Regulation ; Glucose ; Glucose Clamp Technique ; High-fat diet ; Homeostasis ; IL-1 ; IL-1Ra ; Insulin - blood ; Insulin - physiology ; Insulin resistance ; Insulin Resistance - genetics ; Insulin Resistance - physiology ; Interleukin 1 Receptor Antagonist Protein ; interleukin-1 ; Interleukin-1 - physiology ; Interleukin-1 receptor antagonist ; Internal medicine ; Islets of Langerhans - chemistry ; Islets of Langerhans - pathology ; Male ; Medical sciences ; Medicine ; Metabolic diseases ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal - metabolism ; Obesity ; Obesity - etiology ; Obesity - genetics ; Obesity - physiopathology ; Physiology ; Receptors, Interleukin-1 - antagonists & inhibitors ; Receptors, Interleukin-1 - genetics ; Receptors, Interleukin-1 - physiology ; Receptors, Interleukin-1 Type II ; RNA, Messenger - analysis ; RNA, Messenger - genetics ; Rodents ; Sialoglycoproteins - genetics ; Sialoglycoproteins - pharmacology ; Sialoglycoproteins - physiology ; Signal Transduction ; Up-Regulation</subject><ispartof>Diabetologia, 2006-02, Vol.49 (2), p.387-393</ispartof><rights>2006 INIST-CNRS</rights><rights>Springer-Verlag 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-c776475c13c8d15ba57c754edd27e6bb6dee1a005fd579ab9078387da263df9a3</citedby><cites>FETCH-LOGICAL-c423t-c776475c13c8d15ba57c754edd27e6bb6dee1a005fd579ab9078387da263df9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17491649$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16385385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Somm, E</creatorcontrib><creatorcontrib>Cettour-Rose, P</creatorcontrib><creatorcontrib>Asensio, C</creatorcontrib><creatorcontrib>Charollais, A</creatorcontrib><creatorcontrib>Klein, M</creatorcontrib><creatorcontrib>Theander-Carrillo, C</creatorcontrib><creatorcontrib>Juge-Aubry, C. E</creatorcontrib><creatorcontrib>Dayer, J. -M</creatorcontrib><creatorcontrib>Nicklin, M. J. H</creatorcontrib><creatorcontrib>Meda, P</creatorcontrib><creatorcontrib>Rohner-Jeanrenaud, F</creatorcontrib><creatorcontrib>Meier, C. A</creatorcontrib><title>Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><description>Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn -/- animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn -/- animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.</description><subject>Adipose Tissue - physiopathology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - analysis</subject><subject>Body fat</subject><subject>Cytokines</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet</subject><subject>Dietary Fats - adverse effects</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation</subject><subject>Glucose</subject><subject>Glucose Clamp Technique</subject><subject>High-fat diet</subject><subject>Homeostasis</subject><subject>IL-1</subject><subject>IL-1Ra</subject><subject>Insulin - blood</subject><subject>Insulin - physiology</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - genetics</subject><subject>Insulin Resistance - physiology</subject><subject>Interleukin 1 Receptor Antagonist Protein</subject><subject>interleukin-1</subject><subject>Interleukin-1 - physiology</subject><subject>Interleukin-1 receptor antagonist</subject><subject>Internal medicine</subject><subject>Islets of Langerhans - chemistry</subject><subject>Islets of Langerhans - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Metabolic diseases</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - genetics</subject><subject>Obesity - physiopathology</subject><subject>Physiology</subject><subject>Receptors, Interleukin-1 - antagonists & inhibitors</subject><subject>Receptors, Interleukin-1 - genetics</subject><subject>Receptors, Interleukin-1 - physiology</subject><subject>Receptors, Interleukin-1 Type II</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - genetics</subject><subject>Rodents</subject><subject>Sialoglycoproteins - genetics</subject><subject>Sialoglycoproteins - pharmacology</subject><subject>Sialoglycoproteins - physiology</subject><subject>Signal Transduction</subject><subject>Up-Regulation</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdkV1rFTEQhoNY7LH6A7zRUNC71Xxn91JK1ULBCy14F7LJ7CF1T_aYD-n592Y5RwqFDCEzzzsZ5kXoDSUfKSH6UyaEMtkRsoZQ3cMztKGCs44I1j9Hm7Xc0V79Okcvc74nhHAp1At0ThXvZTsbdLiJBdIM9XeIHcUJHOzLkrCNxW6XGHLBIeO6T7Ctsy3gsa8pxC32AUoXoq-u5ZYRciiHpvL4P5lxiLnOIeIMsVXD35Voz7R4iCW_QmeTnTO8Pt0X6O7L9c-rb93t9683V59vOycYL53TWgktHeWu91SOVmqnpQDvmQY1jsoDUNtWMHmpBzsORPe8194yxf00WH6BPhz77tPyp0IuZheyg3m2EZaajdKKDUIODbx8At4vNcU2m2G0LYtotkL0CLm05JxgMvsUdjYdDCVmNcUcTTFtIrOaYh6a5u2pcR134B8VJxca8P4E2OzsPCUbXciPnBYDVWL9_N2Rm-xi7DY15u4HI5QT0steqYH_A4ysoL8</recordid><startdate>20060201</startdate><enddate>20060201</enddate><creator>Somm, E</creator><creator>Cettour-Rose, P</creator><creator>Asensio, C</creator><creator>Charollais, A</creator><creator>Klein, M</creator><creator>Theander-Carrillo, C</creator><creator>Juge-Aubry, C. E</creator><creator>Dayer, J. -M</creator><creator>Nicklin, M. J. H</creator><creator>Meda, P</creator><creator>Rohner-Jeanrenaud, F</creator><creator>Meier, C. A</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20060201</creationdate><title>Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents</title><author>Somm, E ; Cettour-Rose, P ; Asensio, C ; Charollais, A ; Klein, M ; Theander-Carrillo, C ; Juge-Aubry, C. E ; Dayer, J. -M ; Nicklin, M. J. H ; Meda, P ; Rohner-Jeanrenaud, F ; Meier, C. A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-c776475c13c8d15ba57c754edd27e6bb6dee1a005fd579ab9078387da263df9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adipose Tissue - physiopathology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - analysis</topic><topic>Body fat</topic><topic>Cytokines</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet</topic><topic>Dietary Fats - adverse effects</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation</topic><topic>Glucose</topic><topic>Glucose Clamp Technique</topic><topic>High-fat diet</topic><topic>Homeostasis</topic><topic>IL-1</topic><topic>IL-1Ra</topic><topic>Insulin - blood</topic><topic>Insulin - physiology</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - genetics</topic><topic>Insulin Resistance - physiology</topic><topic>Interleukin 1 Receptor Antagonist Protein</topic><topic>interleukin-1</topic><topic>Interleukin-1 - physiology</topic><topic>Interleukin-1 receptor antagonist</topic><topic>Internal medicine</topic><topic>Islets of Langerhans - chemistry</topic><topic>Islets of Langerhans - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Metabolic diseases</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Obesity</topic><topic>Obesity - etiology</topic><topic>Obesity - genetics</topic><topic>Obesity - physiopathology</topic><topic>Physiology</topic><topic>Receptors, Interleukin-1 - antagonists & inhibitors</topic><topic>Receptors, Interleukin-1 - genetics</topic><topic>Receptors, Interleukin-1 - physiology</topic><topic>Receptors, Interleukin-1 Type II</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - genetics</topic><topic>Rodents</topic><topic>Sialoglycoproteins - genetics</topic><topic>Sialoglycoproteins - pharmacology</topic><topic>Sialoglycoproteins - physiology</topic><topic>Signal Transduction</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Somm, E</creatorcontrib><creatorcontrib>Cettour-Rose, P</creatorcontrib><creatorcontrib>Asensio, C</creatorcontrib><creatorcontrib>Charollais, A</creatorcontrib><creatorcontrib>Klein, M</creatorcontrib><creatorcontrib>Theander-Carrillo, C</creatorcontrib><creatorcontrib>Juge-Aubry, C. E</creatorcontrib><creatorcontrib>Dayer, J. -M</creatorcontrib><creatorcontrib>Nicklin, M. J. H</creatorcontrib><creatorcontrib>Meda, P</creatorcontrib><creatorcontrib>Rohner-Jeanrenaud, F</creatorcontrib><creatorcontrib>Meier, C. 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E</au><au>Dayer, J. -M</au><au>Nicklin, M. J. H</au><au>Meda, P</au><au>Rohner-Jeanrenaud, F</au><au>Meier, C. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents</atitle><jtitle>Diabetologia</jtitle><addtitle>Diabetologia</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>49</volume><issue>2</issue><spage>387</spage><epage>393</epage><pages>387-393</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn -/- animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn -/- animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5 days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistance.</abstract><cop>Berlin</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>16385385</pmid><doi>10.1007/s00125-005-0046-x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose Tissue - physiopathology Animals Biological and medical sciences Blood Glucose - analysis Body fat Cytokines Diabetes. Impaired glucose tolerance Diet Dietary Fats - adverse effects Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Deletion Gene Expression Regulation Glucose Glucose Clamp Technique High-fat diet Homeostasis IL-1 IL-1Ra Insulin - blood Insulin - physiology Insulin resistance Insulin Resistance - genetics Insulin Resistance - physiology Interleukin 1 Receptor Antagonist Protein interleukin-1 Interleukin-1 - physiology Interleukin-1 receptor antagonist Internal medicine Islets of Langerhans - chemistry Islets of Langerhans - pathology Male Medical sciences Medicine Metabolic diseases Metabolism Mice Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal - metabolism Obesity Obesity - etiology Obesity - genetics Obesity - physiopathology Physiology Receptors, Interleukin-1 - antagonists & inhibitors Receptors, Interleukin-1 - genetics Receptors, Interleukin-1 - physiology Receptors, Interleukin-1 Type II RNA, Messenger - analysis RNA, Messenger - genetics Rodents Sialoglycoproteins - genetics Sialoglycoproteins - pharmacology Sialoglycoproteins - physiology Signal Transduction Up-Regulation |
| title | Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents |
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