{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:16:22Z","timestamp":1785752182522,"version":"3.56.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"5","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK017047"],"award-info":[{"award-number":["P30DK017047"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1RR025014"],"award-info":[{"award-number":["UL1RR025014"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Total insulin clearance is decreased in nonalcoholic fatty liver disease (NAFLD), but the relationship between liver fat and hepatic insulin extraction (HIE) is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This cross-sectional study addresses the hypothesis that HIE is reduced in NAFLD and investigates metabolic and\/or anthropometric characteristics most closely associated with insulin clearance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Nondiabetic subjects with NAFLD (n = 13) and age- and body mass index (BMI)-matched controls with normal liver enzymes (n = 15) underwent abdominal CT, dual-energy X-ray absorptiometry, oral glucose tolerance test (OGTT), and labeled two-step hyperinsulinemic-euglycemic clamps.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcome Measurements<\/jats:title>\n                  <jats:p>Liver fat was estimated by the CT liver\/spleen ratio. Hepatic and extrahepatic insulin clearances were modeled using clamp and OGTT data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Extrahepatic insulin clearance and HIE were not different between NAFLD and controls and did not correlate with liver fat. HIE was positively correlated with insulin sensitivity [rate of glucose disposal (Rd; low r = +0.7, P &amp;lt; 0.001; high r = +0.6, P = 0.001), adiponectin (r = +0.55, P = 0.004), and insulin-mediated suppression of clamp nonesterified free fatty acid (NEFA; r = +0.67, P &amp;lt; 0.001)] but was not associated with fasting NEFA, insulin-mediated suppression of glucose production, or measures of adiposity. Extrahepatic insulin clearance was positively associated with percent body fat (r = +0.44, P = 0.02) and subcutaneous fat (r = +0.42, P = 0.03) but not BMI, intra-abdominal fat, liver fat, Rd, adiponectin, or NEFA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HIE is not directly associated with hepatic steatosis but is associated with muscle and adipose tissue insulin resistance. The data suggest differential regulation of insulin clearance with extrahepatic insulin clearance being associated with body fat and not insulin sensitivity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2018-01808","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T19:31:22Z","timestamp":1545247882000},"page":"1855-1865","source":"Crossref","is-referenced-by-count":58,"title":["Hepatic Insulin Extraction in NAFLD Is Related to Insulin Resistance Rather Than Liver Fat Content"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-196X","authenticated-orcid":false,"given":"Kristina M","family":"Utzschneider","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Hospital Specialty Medicine, VA Puget Sound Health Care System, Seattle, Washington"},{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Hospital Specialty Medicine, VA Puget Sound Health Care System, Seattle, Washington"},{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Polidori","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"issue":"7121","key":"2020071622400683700_B1","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"issue":"1","key":"2020071622400683700_B2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev.me.24.020173.001521","article-title":"Extraction of insulin by liver","volume":"24","author":"Field","year":"1973","journal-title":"Annu Rev Med"},{"issue":"6","key":"2020071622400683700_B3","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.2337\/diabetes.54.6.1649","article-title":"Pulsatile insulin secretion dictates systemic insulin delivery by regulating hepatic insulin extraction in humans","volume":"54","author":"Meier","year":"2005","journal-title":"Diabetes"},{"issue":"6","key":"2020071622400683700_B4","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1172\/JCI112758","article-title":"Splanchnic insulin metabolism in obesity. 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