{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:54:00Z","timestamp":1790553240718,"version":"4.1.0"},"reference-count":43,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Resistin, an adipocyte secreted factor, has been suggested to link obesity with type 2 diabetes in rodent models, but its relevance to human diabetes remains uncertain. Although previous studies have suggested a role for this adipocytokine as a pathogenic factor, its functional effects, regulation by insulin, and alteration of serum resistin concentration by diabetes status remain to be elucidated. Therefore, the aims of this study were to analyze serum resistin concentrations in type 2 diabetic subjects; to determine the in vitro effects of insulin and rosiglitazone (RSG) on the regulation of resistin, and to examine the functional effects of recombinant human resistin on glucose and lipid metabolism in vitro. Serum concentrations of resistin were analyzed in 45 type 2 diabetic subjects and 34 nondiabetic subjects. Subcutaneous human adipocytes were incubated in vitro with insulin, RSG, and insulin in combination with RSG to examine effects on resistin secretion. Serum resistin was increased by approximately 20% in type 2 diabetic subjects compared with nondiabetic subjects (P = 0.004) correlating with C-reactive protein. No other parameters, including adiposity and fasting insulin levels, correlated with serum resistin in this cohort. However, in vitro, insulin stimulated resistin protein secretion in a concentration-dependent manner in adipocytes [control, 1215 \u00b1 87 pg\/ml (mean \u00b1 sem); 1 nm insulin, 1414.0 \u00b1 89 pg\/ml; 1 \u03bcm insulin, 1797 \u00b1 107 pg\/ml (P &amp;lt; 0.001)]. RSG (10 nm) reduced the insulin-mediated rise in resistin protein secretion (1 nm insulin plus RSG, 971 \u00b1 35 pg\/ml; insulin, 1 \u03bcm insulin plus RSG, 1019 \u00b1 28 pg\/ml; P &amp;lt; 0.01 vs. insulin alone). Glucose uptake was reduced after treatment with 10 ng\/ml recombinant resistin and higher concentrations (P &amp;lt; 0.05). Our in vitro studies demonstrated a small, but significant, reduction in glucose uptake with human recombinant resistin in differentiated preadipocytes. In human abdominal sc adipocytes, RSG blocks the insulin-mediated release of resistin secretion in vitro. In conclusion, elevated serum resistin in human diabetes reflects the subclinical inflammation prevalent in type 2 diabetes. Our in vitro studies suggest a modest effect of resistin in reducing glucose uptake, and suppression of resistin expression may contribute to the insulin-sensitizing and glucose-lowering actions of the thiazolidinediones.<\/jats:p>","DOI":"10.1210\/jc.2003-030898","type":"journal-article","created":{"date-parts":[[2003,12,11]],"date-time":"2003-12-11T22:23:51Z","timestamp":1071181431000},"page":"6098-6106","source":"Crossref","is-referenced-by-count":211,"title":["Resistin and Type 2 Diabetes: Regulation of Resistin Expression by Insulin and Rosiglitazone and the Effects of Recombinant Resistin on Lipid and Glucose Metabolism in Human Differentiated Adipocytes"],"prefix":"10.1210","volume":"88","author":[{"given":"Philip G.","family":"McTernan","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FFolliott M.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Valsamakis","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajkumar","family":"Chetty","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Harte","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"McTernan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny M. S.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Glaxo-SmithKline, New Frontiers Science Park (S.A.S.), Harlow, United Kingdom CM19 5AW"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Birmingham and Heartlands Hospital (P.G.M., F.M.F., G.V., R.C., A.H., C.L.M., P.M.S.C., A.H.B., S.K.), Edgbaston Birmingham, United Kingdom B15 2TH;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614002081900_R1","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1093\/emboj\/19.15.4046","article-title":"FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family.","volume":"19","author":"Holcomb","year":"2000","journal-title":"EMBO J"},{"key":"2020071614002081900_R2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/35053000","article-title":"The hormone resistin links obesity to diabetes.","volume":"409","author":"Steppan","year":"2001","journal-title":"Nature"},{"key":"2020071614002081900_R3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1073\/pnas.98.2.502","article-title":"A family of tissue-specific resistin like molecules.","volume":"98","author":"Steppan","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614002081900_R4","doi-asserted-by":"crossref","first-page":"11252","DOI":"10.1074\/jbc.C100028200","article-title":"A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation.","volume":"276","author":"Kim","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071614002081900_R5","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1006\/bbrc.2001.6015","article-title":"Decreased resistin expression in mice with different sensitivities to a high-fat diet.","volume":"289","author":"Lay","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614002081900_R6","doi-asserted-by":"crossref","first-page":"E626","DOI":"10.1152\/ajpendo.00346.2001","article-title":"Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats","volume":"282","author":"Levy","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071614002081900_R7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0014-5793(01)02968-4","article-title":"Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes.","volume":"507","author":"Haugen","year":"2001","journal-title":"FEBS Lett"},{"key":"2020071614002081900_R8","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.2337\/diabetes.50.10.2199","article-title":"Resistin\/FIZZ3 expression in relation to obesity and peroxisome proliferator-activated receptor-\u03b3 action in humans.","volume":"50","author":"Savage","year":"2001","journal-title":"Diabetes"},{"key":"2020071614002081900_R9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1006\/bbrc.2001.5173","article-title":"Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle.","volume":"285","author":"Nagaev I and Smith","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614002081900_R10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/oby.2002.1","article-title":"Resistin gene expression in human adipocytes is not related to insulin resistance.","volume":"10","author":"Engeli","year":"2002","journal-title":"Obes Res"},{"key":"2020071614002081900_R11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0140-6736(02)07281-1","article-title":"Resistin central obesity and type 2 diabetes.","volume":"35","author":"McTernan","year":"2002","journal-title":"Lancet"},{"key":"2020071614002081900_R12","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1210\/jcem.87.5.8627","article-title":"Increased resistin gene and protein expression in human abdominal adipose tissue.","volume":"87","author":"McTernan","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614002081900_R13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S1043-2760(01)00522-7","article-title":"Resistin and obesity-associated insulin resistance.","volume":"13","author":"Steppan","year":"2002","journal-title":"Trends Endocrinol Metab"},{"key":"2020071614002081900_R14","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1006\/bbrc.2001.5460","article-title":"Differential regulation of adipocytokine mRNA by rosiglitazone in db\/db mice.","volume":"286","author":"Moore","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614002081900_R15","doi-asserted-by":"crossref","first-page":"25651","DOI":"10.1074\/jbc.C100189200","article-title":"Adipose tissue resistin expression is severely suppressed in obesity and stimulated by PPAR\u03b3 agonists.","volume":"276","author":"Way","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071614002081900_R16","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentration in man.","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2020071614002081900_R17","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/sj.ijo.0801254","article-title":"Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue.","volume":"24","author":"McTernan","year":"2000","journal-title":"Int J Obes Relat Metabol Disord"},{"key":"2020071614002081900_R18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0014-4827(87)90412-5","article-title":"Development of a chemically defined, serum-free medium for differentiation of rat adipose precursor cells.","volume":"168","author":"Deslex","year":"1987","journal-title":"Exp Cell Res"},{"key":"2020071614002081900_R19","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1172\/JCI114345","article-title":"Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium.","volume":"84","author":"Hauner","year":"1989","journal-title":"J Clin Invest"},{"key":"2020071614002081900_R20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1677\/joe.0.1560135","article-title":"Hormone induced changes in nuclear receptor stoichiometry in HL60 cells correlate with induction of monocyte or neutrophil differentiation.","volume":"156","author":"McTernan","year":"1998","journal-title":"J Endocrinol"},{"key":"2020071614002081900_R21","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.2337\/diabetes.51.5.1493","article-title":"Long-term insulin and rosiglitazone mediated regulation of LPL, HSL, lipolysis in human adipose tissue.","volume":"51","author":"McTernan","year":"2002","journal-title":"Diabetes"},{"key":"2020071614002081900_R22","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"2020071614002081900_R23","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1016\/S0021-9258(19)76920-8","article-title":"Microdetermination of long-chain fatty acids in plasma and tissues.","volume":"235","author":"Dole","year":"1960","journal-title":"J Biol Chem"},{"key":"2020071614002081900_R24","volume-title":"Handbook of histopathological techniques, 2nd Ed","author":"Culling","year":"1963"},{"key":"2020071614002081900_R25","first-page":"4979","article-title":"Reduced placental 11\u03b2-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms.","volume":"86","author":"McTernan","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614002081900_R26","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2165\/00003495-199957060-00007","article-title":"Rosiglitazone.","volume":"57","author":"Balfour","year":"1999","journal-title":"Drugs"},{"key":"2020071614002081900_R27","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1749-6632.2002.tb04293.x","article-title":"Leptin signalling, adiposity and energy balance.","volume":"967","author":"Jequier","year":"2000","journal-title":"Ann NY Acad Sci"},{"key":"2020071614002081900_R28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1046\/j.1365-2265.2000.00921.x","article-title":"The innate immune response and type 2 diabetes: evidence that leptin is associated with stress-related (acute-phase) reaction.","volume":"52","author":"Pickup","year":"2000","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"Suppl 2","key":"2020071614002081900_R29","first-page":"A405","article-title":"Serum resistin is significantly elevated in obese humans","volume":"51","author":"Degawa-Yamauchi","year":"2002","journal-title":"Diabetes"},{"key":"2020071614002081900_R30","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1210\/jcem.87.6.8528","article-title":"Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians.","volume":"87","author":"Wang","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614002081900_R31","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.2337\/diabetes.51.5.1629","article-title":"5\u2032 flanking variants of resistin are associated with obesity.","volume":"51","author":"Engert","year":"2002","journal-title":"Diabetes"},{"key":"2020071614002081900_R32","doi-asserted-by":"crossref","first-page":"863","DOI":"10.2337\/diabetes.51.3.863","article-title":"Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes.","volume":"51","author":"Osawa","year":"2002","journal-title":"Diabetes"},{"key":"2020071614002081900_R33","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1210\/me.2002-0048","article-title":"Cell type-specific expression and co-regulation of murine molecule-\u03b1 in adipose tissue.","volume":"16","author":"Rajala","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071614002081900_R34","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0014-5793(02)03450-6","article-title":"Lipolysaccharide increases resistin gene expression in vivo and in vitro.","volume":"530","author":"Lu","year":"2002","journal-title":"FEBS Lett"},{"key":"2020071614002081900_R35","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1172\/JCI10843","article-title":"Treatment of insulin resistance with peroxisome proliferator-activated receptor \u03b3 agonists.","volume":"106","author":"Olefsky","year":"2000","journal-title":"J Clin Invest"},{"key":"2020071614002081900_R36","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.2337\/diabetes.50.5.1126","article-title":"Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys.","volume":"50","author":"Hotta","year":"2001","journal-title":"Diabetes"},{"key":"2020071614002081900_R37","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.2337\/diab.45.12.1661","article-title":"Thiazolidinediones in the treatment of insulin resistance and type 2 diabetes.","volume":"45","author":"Saltiel","year":"1996","journal-title":"Diabetes"},{"key":"2020071614002081900_R38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S0006-291X(02)02841-3","article-title":"Resistin is expressed in human macrophages and directly regulated by PPAR\u03b3 activators.","volume":"300","author":"Patel","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614002081900_R39","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/BF00418542","article-title":"Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone study group.","volume":"39","author":"Kumar","year":"1996","journal-title":"Diabetologia"},{"key":"2020071614002081900_R40","first-page":"393","article-title":"Enhancement of adipocyte differentiation by an insulin-sensitizing agent.","volume":"41","author":"Kletzien","year":"1992","journal-title":"Mol Pharmacol"},{"key":"2020071614002081900_R41","first-page":"306","article-title":"Do resistin and resistin-like molecules also link obesity to inflammatory disease?","volume":"4","author":"Gomez-Ambrosi","year":"2002","journal-title":"Ann Intern Med"},{"key":"2020071614002081900_R42","first-page":"2235","article-title":"Chronic systemic inflammation in overweight and obese adults.","volume":"283","author":"Vgontzas","year":"2000","journal-title":"JAMA"},{"key":"2020071614002081900_R43","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S1043-2760(00)00272-1","article-title":"Potential role of TNF-\u03b1 in the pathogenesis of insulin resistance and type 2 diabetes.","volume":"11","author":"Moller","year":"2000","journal-title":"Trends Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/12\/6098\/9065758\/jcem6098.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/12\/6098\/9065758\/jcem6098.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T13:24:17Z","timestamp":1623590657000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/88\/12\/6098\/2661530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12,1]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2003,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2003-030898","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12,1]]}}}