{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:07:56Z","timestamp":1782331676543,"version":"3.54.5"},"reference-count":33,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK40484"],"award-info":[{"award-number":["DK40484"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK45343"],"award-info":[{"award-number":["DK45343"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Adipose tissue (AT) lipolysis insulin resistance results in excess free fatty acid (FFA) release. We tested the hypothesis that the ability of insulin to suppress AT lipolysis is unrelated to the ability of niacin to suppress lipolysis, because niacin acts through a different proximal signaling pathway. Ten volunteers (5 women and 5 men) with upper-body obesity and\/or type 2 diabetes mellitus (T2DM) underwent two study visits with overnight intravenous infusions of niacin (1.4 mg\/min) or saline, followed by a hyperinsulinemic-euglycemic clamp. FFA-palmitate Ra was measured using [U-13C] and [2H9]palmitate infusions; abdominal AT biopsies were performed before and during the insulin clamp. The suppression of FFA-palmitate Ra by insulin on the saline control day and by niacin after an overnight infusion were highly correlated (r = \u22120.93, P &amp;lt; 0.001). Fasting AT Akt (pAktS473\/474-to-panAkt ratio, P = 0.01) and perilipin 1 (PLN1) (pPLN1S552-to-panPLN1 ratio, P = 0.02) phosphorylation were less during niacin treatment than in the saline control study. Because the suppression of lipolysis by insulin and niacin are highly correlated within individuals and because niacin and insulin act through different proximal signaling pathways, we propose dysregulated AT lipolysis in obesity\/T2DM is due to dysfunction(s) in distal lipolysis proteins rather than isolated \u201cinsulin resistance.\u201d<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>We undertook this study to compare adipose tissue lipolysis responses to insulin and niacin in humans. We tested the hypothesis that adipose tissue insulin resistance would be unrelated to adipose tissue niacin resistance. The suppression of lipolysis by insulin and niacin were highly correlated. Dysregulated adipose tissue lipolysis in obesity\/type 2 diabetes is due to dysfunction(s) in distal lipolysis proteins rather than isolated \u201cinsulin resistance.\u201d<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0979","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:30:33Z","timestamp":1771349433000},"page":"636-645","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["Adipose Tissue Resistance to the Antilipolytic Effect of Insulin and Niacin in Humans With Obesity"],"prefix":"10.2337","volume":"75","author":[{"given":"Shuhao","family":"Lin","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic 1 , Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli A.","family":"Lytle","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic 1 , Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fink","sequence":"additional","affiliation":[{"name":"Paracelsus Medical University 2 , N\u00fcrnberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-8389","authenticated-orcid":false,"given":"Michael D.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Mayo Clinic 1 , Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"2026061712270599100_B1","doi-asserted-by":"crossref","first-page":"R199","DOI":"10.1530\/JME-13-0277","article-title":"Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease","volume":"52","author":"Nielsen","year":"2014","journal-title":"J Mol Endocrinol"},{"key":"2026061712270599100_B2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diab.38.12.1595","article-title":"Insulin regulation of lipolysis in nondiabetic and IDDM subjects","volume":"38","author":"Jensen","year":"1989","journal-title":"Diabetes"},{"key":"2026061712270599100_B3","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.2337\/diab.42.11.1567","article-title":"Postprandial free fatty acid kinetics are abnormal in upper body obesity","volume":"42","author":"Roust","year":"1993","journal-title":"Diabetes"},{"key":"2026061712270599100_B4","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2796.2005.01528.x","article-title":"Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review","volume":"258","author":"Carlson","year":"2005","journal-title":"J Intern Med"},{"key":"2026061712270599100_B5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0014-5793(80)80715-0","article-title":"Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone\u2013like manner","volume":"115","author":"Aktories","year":"1980","journal-title":"FEBS Lett"},{"key":"2026061712270599100_B6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.metabol.2010.02.013","article-title":"Widespread effects of nicotinic acid on gene expression in insulin-sensitive tissues: implications for unwanted effects of nicotinic acid treatment","volume":"60","author":"Choi","year":"2011","journal-title":"Metabolism"},{"key":"2026061712270599100_B7","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/bmc.1690","article-title":"Simultaneous determination of simvastatin, lovastatin and niacin in human plasma by LC-MS\/MS and its application to a human pharmacokinetic study","volume":"26","author":"Pilli","year":"2012","journal-title":"Biomed Chromatogr"},{"key":"2026061712270599100_B8","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1194\/jlr.M008011","article-title":"Rapid measurement of plasma free fatty acid concentration and isotopic enrichment using LC\/MS","volume":"51","author":"Persson","year":"2010","journal-title":"J Lipid Res"},{"key":"2026061712270599100_B9","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1194\/jlr.D300001-JLR200","article-title":"A quick, reliable, and automated method for fat cell sizing","volume":"44","author":"Tchoukalova","year":"2003","journal-title":"J Lipid Res"},{"key":"2026061712270599100_B10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41387-018-0030-4","article-title":"Human adipose tissue protein analyses using capillary western blot technology","volume":"8","author":"Lu","year":"2018","journal-title":"Nutr Diabetes"},{"key":"2026061712270599100_B11","doi-asserted-by":"crossref","first-page":"e203","DOI":"10.1038\/emm.2015.97","article-title":"Applications of stable, nonradioactive isotope tracers in in vivo human metabolic research","volume":"48","author":"Kim","year":"2016","journal-title":"Exp Mol Med"},{"key":"2026061712270599100_B12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1203\/00006450-198909000-00020","article-title":"Inhibition of lipolysis by agents acting via adenylate cyclase in fat cells from infants and adults","volume":"26","author":"Marcus","year":"1989","journal-title":"Pediatr Res"},{"key":"2026061712270599100_B13","doi-asserted-by":"crossref","first-page":"E59","DOI":"10.1152\/ajpendo.00078.2025","article-title":"Optimizing measures of insulin-regulated lipolysis in humans","volume":"329","author":"Song","year":"2025","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2026061712270599100_B14","doi-asserted-by":"crossref","first-page":"620","DOI":"10.2337\/diab.36.5.620","article-title":"Insulin-receptor kinase activity of adipose tissue from morbidly obese humans with and without NIDDM","volume":"36","author":"Sinha","year":"1987","journal-title":"Diabetes"},{"key":"2026061712270599100_B15","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1006\/bbrc.1993.1143","article-title":"Insulin stimulates the degradation of IRS-1 in 3T3-L1 adipocytes","volume":"190","author":"Rice","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"2026061712270599100_B16","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1172\/JCI112789","article-title":"Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects","volume":"79","author":"Freidenberg","year":"1987","journal-title":"J Clin Invest"},{"key":"2026061712270599100_B17","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.2337\/diabetes.50.11.2563","article-title":"Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state","volume":"50","author":"Teruel","year":"2001","journal-title":"Diabetes"},{"key":"2026061712270599100_B18","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1128\/MCB.00422-15","article-title":"The role of PDE3B phosphorylation in the inhibition of lipolysis by insulin","volume":"35","author":"DiPilato","year":"2015","journal-title":"Mol Cell Biol"},{"key":"2026061712270599100_B19","doi-asserted-by":"crossref","first-page":"5009","DOI":"10.1128\/MCB.00797-10","article-title":"Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway","volume":"30","author":"Choi","year":"2010","journal-title":"Mol Cell Biol"},{"key":"2026061712270599100_B20","doi-asserted-by":"crossref","first-page":"6286","DOI":"10.1128\/MCB.19.9.6286","article-title":"Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt","volume":"19","author":"Kitamura","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2026061712270599100_B21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1042\/BJ20060960","article-title":"Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB","volume":"404","author":"Ahmad","year":"2007","journal-title":"Biochem J"},{"key":"2026061712270599100_B22","doi-asserted-by":"crossref","first-page":"101283","DOI":"10.1016\/j.xpro.2022.101283","article-title":"Protocol for analysis of RNA-sequencing and proteome profiling data for subgroup identification and comparison","volume":"3","author":"Yang","year":"2022","journal-title":"STAR Protoc"},{"key":"2026061712270599100_B23","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2337\/diabetes.55.04.06.db05-1414","article-title":"Insulin signaling in human visceral and subcutaneous adipose tissue in vivo","volume":"55","author":"Laviola","year":"2006","journal-title":"Diabetes"},{"key":"2026061712270599100_B24","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1038\/s41366-018-0260-5","article-title":"Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes","volume":"43","author":"Montastier","year":"2019","journal-title":"Int J Obes (Lond)"},{"key":"2026061712270599100_B25","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00125-015-3532-9","article-title":"The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo","volume":"58","author":"Koren","year":"2015","journal-title":"Diabetologia"},{"key":"2026061712270599100_B26","doi-asserted-by":"crossref","first-page":"15011","DOI":"10.1038\/s41598-017-15059-4","article-title":"Visualization of lipid directed dynamics of perilipin 1 in human primary adipocytes","volume":"7","author":"Hansen","year":"2017","journal-title":"Sci Rep"},{"key":"2026061712270599100_B27","doi-asserted-by":"crossref","first-page":"e3756","DOI":"10.1371\/journal.pone.0003756","article-title":"Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates","volume":"3","author":"Krintel","year":"2008","journal-title":"PLoS One"},{"key":"2026061712270599100_B28","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1089\/adt.2010.0302","article-title":"Quantification of hormone sensitive lipase phosphorylation and colocalization with lipid droplets in murine 3T3L1 and human subcutaneous adipocytes via automated digital microscopy and high-content analysis","volume":"9","author":"McDonough","year":"2011","journal-title":"Assay Drug Dev Technol"},{"key":"2026061712270599100_B29","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1074\/jbc.273.1.215","article-title":"Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro","volume":"273","author":"Anthonsen","year":"1998","journal-title":"J Biol Chem"},{"key":"2026061712270599100_B30","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1159\/000334036","article-title":"Relationship between site-specific HSL phosphorylation and adipocyte lipolysis in obese women","volume":"4","author":"Lorente-Cebri\u00e1n","year":"2011","journal-title":"Obes Facts"},{"key":"2026061712270599100_B31","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-nutr-071813-105410","article-title":"The perilipins: major cytosolic lipid droplet-associated proteins and their roles in cellular lipid storage, mobilization, and systemic homeostasis","volume":"36","author":"Kimmel","year":"2016","journal-title":"Annu Rev Nutr"},{"key":"2026061712270599100_B32","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s13318-013-0169-2","article-title":"Gender differences in pharmacokinetics of a combination tablet of niacin extended-release\/simvastatin in healthy Chinese volunteers","volume":"39","author":"Wang","year":"2014","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"2026061712270599100_B33","doi-asserted-by":"crossref","first-page":"212437","DOI":"10.1155\/2015\/212437","article-title":"Quantification of niacin and its metabolite nicotinuric acid in human plasma by LC-MS\/MS: application to a clinical trial of a fixed dose combination tablet of niacin extended-release\/simvastatin (500\u2009mg\/10\u2009mg) in healthy Chinese volunteers","volume":"2015","author":"Zhang","year":"2015","journal-title":"Int J Anal Chem"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/75\/4\/636\/857112\/db250979.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/75\/4\/636\/857112\/db250979.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:27:17Z","timestamp":1781713637000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/75\/4\/636\/164498\/Adipose-Tissue-Resistance-to-the-Antilipolytic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2,17]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db25-0979","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]}}}