{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:56:45Z","timestamp":1791187005231,"version":"4.1.0"},"reference-count":29,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:p>Resistin was originally reported as an adipose tissue\u2013specific hormone that provided a link between obesity and diabetes. Resistin protein level was elevated in obese mice and decreased by insulin-sensitizing thiazolidinediones. Immunoneutralization of resistin improved insulin sensitivity in diet-induced obese mice, while the administration of exogenous resistin induced insulin resistance. More recently, we have shown that ablation of the resistin gene in mice decreased fasting glucose through impairment of gluconeogenesis, while resistin treatment in these knockout mice increased hepatic glucose production. However, the link between resistin and glucose homeostasis has been questioned by studies demonstrating reduced, rather than increased, resistin mRNA expression in obese and diabetic mice. To better understand the regulation of resistin, we developed a sensitive and specific RIA resistin that could accurately measure serum resistin levels in several mouse models. We show that while resistin mRNA is indeed suppressed in obese mice, the circulating resistin level is significantly elevated and positively correlated with insulin, glucose, and lipids. Both resistin mRNA expression and protein levels in Lepob\/ob mice are suppressed by leptin treatment in parallel with reductions in glucose and insulin. In wild-type mice, serum resistin increases after nocturnal feeding, concordant with rising levels of insulin. Resistin mRNA and protein levels decline in parallel with glucose and insulin during fasting and are restored after refeeding. We performed clamp studies to determine whether resistin is causally related to insulin and glucose. Adipose resistin expression and serum resistin increased in response to hyperinsulinemia and further in response to hyperglycemia. Taken together, these findings suggest that the nutritional regulation of resistin and changes in resistin gene expression and circulating levels in obesity are mediated, at least in part, through insulin and glucose.<\/jats:p>","DOI":"10.2337\/diabetes.53.7.1671","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T14:04:22Z","timestamp":1173189862000},"page":"1671-1679","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":274,"title":["Regulation of Resistin Expression and Circulating Levels in Obesity, Diabetes, and Fasting"],"prefix":"10.2337","volume":"53","author":[{"given":"Michael W.","family":"Rajala","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiral R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronadip","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal B.","family":"Pajvani","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhur K.","family":"Sinha","sequence":"additional","affiliation":[{"name":"Linco Research, St. Charles, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Gingerich","sequence":"additional","affiliation":[{"name":"Linco Research, St. Charles, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp E.","family":"Scherer","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rexford S.","family":"Ahima","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209420027500_R1","doi-asserted-by":"crossref","unstructured":"Kahn BB, Flier JS: Obesity and insulin resistance. J Clin Invest\u2008106:473\u2013481,2000","DOI":"10.1172\/JCI10842"},{"key":"2022031209420027500_R2","doi-asserted-by":"crossref","unstructured":"Ahima RS, Flier JS: Adipose tissue as an endocrine organ. Trends Endocrinol Metab\u200811:327\u2013332,2000","DOI":"10.1016\/S1043-2760(00)00301-5"},{"key":"2022031209420027500_R3","doi-asserted-by":"crossref","unstructured":"Kim JK, Fillmore JJ, Gavrilova O, Chao L, Higashimori T, Choi H, Kim HJ, Yu C, Chen Y, Qu X, Haluzik M, Reitman ML, Shulman GI: Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance in A-ZIP\/F-1 fatless mice. Diabetes\u200852:1311\u20131318,2003","DOI":"10.2337\/diabetes.52.6.1311"},{"key":"2022031209420027500_R4","doi-asserted-by":"crossref","unstructured":"Rajala MW, Scherer PE: Minireview: the adipocyte\u2014at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology\u2008144:3765\u20133773,2003","DOI":"10.1210\/en.2003-0580"},{"key":"2022031209420027500_R5","doi-asserted-by":"crossref","unstructured":"Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature\u2008409:307\u2013312,2001","DOI":"10.1038\/35053000"},{"key":"2022031209420027500_R6","doi-asserted-by":"crossref","unstructured":"Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA: A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci U S A\u200898:502\u2013506,2001","DOI":"10.1073\/pnas.98.2.502"},{"key":"2022031209420027500_R7","doi-asserted-by":"crossref","unstructured":"Holcomb IN, Kabakoff RC, Chan B, Baker TW, Gurney A, Henzel W, Nelson C, Lowman HB, Wright BD, Skelton NJ, Frantz GD, Tumas DB, Peale FV Jr, Shelton DL, Hebert CC: FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J\u200819:4046\u20134055,2000","DOI":"10.1093\/emboj\/19.15.4046"},{"key":"2022031209420027500_R8","doi-asserted-by":"crossref","unstructured":"Rajala MW, Obici S, Scherer PE, Rossetti L: Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest\u2008111:225\u2013230,2003","DOI":"10.1172\/JCI16521"},{"key":"2022031209420027500_R9","doi-asserted-by":"crossref","unstructured":"Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA: Regulation of fasted blood glucose by resistin. Science\u2008303:1195\u20131198,2004","DOI":"10.1126\/science.1092341"},{"key":"2022031209420027500_R10","doi-asserted-by":"crossref","unstructured":"Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS: Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem\u2008276:25651\u201325653,2001","DOI":"10.1074\/jbc.C100189200"},{"key":"2022031209420027500_R11","doi-asserted-by":"crossref","unstructured":"Rajala MW, Lin Y, Ranalletta M, Yang XM, Qian H, Gingerich R, Barzilai N, Scherer PE: Cell type-specific expression and coregulation of murine resistin and resistin-like molecule-alpha in adipose tissue. Mol Endocrinol\u200816:1920\u20131930,2003","DOI":"10.1210\/me.2002-0048"},{"key":"2022031209420027500_R12","doi-asserted-by":"crossref","unstructured":"Kim KH, Lee K, Moon YS, Sul HS: A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem\u2008276:11252\u201311256,2001","DOI":"10.1074\/jbc.C100028200"},{"key":"2022031209420027500_R13","doi-asserted-by":"crossref","unstructured":"Banerjee RR, Lazar MA: Resistin: molecular history and prognosis. J Mol Med\u200881:218\u2013226,2003","DOI":"10.1007\/s00109-003-0428-9"},{"key":"2022031209420027500_R14","doi-asserted-by":"crossref","unstructured":"Burant CF, Sreenan S, Hirano K, Tai TA, Lohmiller J, Lukens J, Davidson NO, Ross S, Graves RA: Troglitazone action is independent of adipose tissue. J Clin Invest\u2008100:2900\u20132908,1997","DOI":"10.1172\/JCI119839"},{"key":"2022031209420027500_R15","doi-asserted-by":"crossref","unstructured":"Berg AH, Combs TP, Du X, Brownlee M, Scherer PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med\u20087:947\u2013953,2001","DOI":"10.1038\/90992"},{"key":"2022031209420027500_R16","doi-asserted-by":"crossref","unstructured":"Takahashi N, Patel HR, Qi Y, Dushay J, Ahima RS: Divergent effects of leptin in mice susceptible or resistant to obesity. Horm Metab Res\u200834:691\u2013697,2002","DOI":"10.1055\/s-2002-38251"},{"key":"2022031209420027500_R17","doi-asserted-by":"crossref","unstructured":"Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS: Role of leptin in the neuroendocrine response to fasting. Nature\u2008382:250\u2013252,1996","DOI":"10.1038\/382250a0"},{"key":"2022031209420027500_R18","doi-asserted-by":"crossref","unstructured":"Van Heek M, Compton DS, France CF, Tedesco RP, Fawzi AB, Graziano MP, Sybertz EJ, Strader CD, Davis HR Jr: Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest\u200899:385\u2013390,1997","DOI":"10.1172\/JCI119171"},{"key":"2022031209420027500_R19","doi-asserted-by":"crossref","unstructured":"Nagy TR, Clair AL: Precision and accuracy of dual-energy X-ray absorptiometry for determining in vivo body composition of mice. Obes Res\u20088:392\u2013398,2000","DOI":"10.1038\/oby.2000.47"},{"key":"2022031209420027500_R20","doi-asserted-by":"crossref","unstructured":"Ahima RS, Bjorbaek C, Osei S, Flier JS: Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinology\u2008140:2755\u20132762,1999","DOI":"10.1210\/endo.140.6.6774"},{"key":"2022031209420027500_R21","doi-asserted-by":"crossref","unstructured":"Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science\u2008269:543\u2013546,1995","DOI":"10.1126\/science.7624777"},{"key":"2022031209420027500_R22","doi-asserted-by":"crossref","unstructured":"Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob\/ob mice. Science\u2008269:540\u2013543,1995","DOI":"10.1126\/science.7624776"},{"key":"2022031209420027500_R23","doi-asserted-by":"crossref","unstructured":"Pravenec M, Kazdova L, Landa V, Zidek V, Mlejnek P, Jansa P, Wang J, Qi N, Kurtz TW: Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat. J Biol Chem\u2008278:45209\u201345215,2003","DOI":"10.1074\/jbc.M304869200"},{"key":"2022031209420027500_R24","doi-asserted-by":"crossref","unstructured":"Moon B, Kwan JJ, Duddy N, Sweeney G, Begum N: Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab\u2008285:E106\u2013E115,2003","DOI":"10.1152\/ajpendo.00457.2002"},{"key":"2022031209420027500_R25","doi-asserted-by":"crossref","unstructured":"Huang L, Wang Z, Li C: Modulation of circulating leptin levels by its soluble receptor. J Biol Chem\u2008276:6343\u20136349,2001","DOI":"10.1074\/jbc.M009795200"},{"key":"2022031209420027500_R26","doi-asserted-by":"crossref","unstructured":"Lahlou N, Clement K, Carel JC, Vaisse C, Lotton C, Le Bihan Y, Basdevant A, Lebouc Y, Froguel P, Roger M, Guy-Grand B: Soluble leptin receptor in serum of subjects with complete resistance to leptin: relation to fat mass. Diabetes\u200849:1347\u20131352,2002","DOI":"10.2337\/diabetes.49.8.1347"},{"key":"2022031209420027500_R27","doi-asserted-by":"crossref","unstructured":"Winkler G, Kiss S, Keszthelyi L, Sapi Z, Ory I, Salamon F, Kovacs M, Vargha P, Szekeres O, Speer G, Karadi I, Sikter M, Kaszas E, Dworak O, Gero G, Cseh K: Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. Eur J Endocrinol\u2008149:129\u2013135,2003","DOI":"10.1530\/eje.0.1490129"},{"key":"2022031209420027500_R28","doi-asserted-by":"crossref","unstructured":"Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P: Changes of glycemia by leptin administration or high fat feeding in rodent models of obesity\/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology\u2008145:2206\u20132213,2004","DOI":"10.1210\/en.2003-1679"},{"key":"2022031209420027500_R29","doi-asserted-by":"crossref","unstructured":"Maebuchi M, Machidori M, Urade R, Ogawa T, Moriyama T: Low resistin levels in adipose tissues and serum in high-fat fed mice and genetically obese mice: development of an ELISA system for quantification of resistin. Arch Biochem Biophys\u2008416:164\u2013170,2003","DOI":"10.1016\/S0003-9861(03)00279-0"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/53\/7\/1671\/652102\/zdb00704001671.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/53\/7\/1671\/652102\/zdb00704001671.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T12:22:34Z","timestamp":1667391754000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/53\/7\/1671\/14332\/Regulation-of-Resistin-Expression-and-Circulating"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,1]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2004,7,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.53.7.1671","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,1]]}}}