{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:32:39Z","timestamp":1792006359782,"version":"4.4.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK24092"],"award-info":[{"award-number":["DK24092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To examine the relationship between plasma glucagon levels and insulin sensitivity and insulin secretion in obese subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Suppression of plasma glucagon was examined in 275 obese Hispanic Americans with varying glucose tolerance. All subjects received a 2-hour oral glucose tolerance test (OGTT) and a subset (n = 90) had euglycemic hyperinsulinemic clamp. During OGTT, we quantitated suppression of plasma glucagon concentration, Matsuda index of insulin sensitivity, and insulin secretion\/insulin resistance (disposition) index. Plasma glucagon suppression was compared between quartiles of insulin sensitivity and beta-cell function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fasting plasma glucagon levels were similar in obese subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes (T2D), but the fasting glucagon\/insulin ratio decreased progressively from NGT to prediabetes to T2D (9.28 \u00b1 0.66 vs 6.84 \u00b1 0.44 vs 5.84 \u00b1 0.43; P &amp;lt; 0.001). Fasting and 2-hour plasma glucagon levels during OGTT progressively increased and correlated positively with severity of insulin resistance (both Matsuda index and euglycemic hyperinsulinemic clamp). The fasting glucagon\/insulin ratio declined with worsening insulin sensitivity and beta-cell function, and correlated with whole-body insulin sensitivity (Matsuda index, r = 0.81; P &amp;lt; 0.001) and beta-cell function (r = 0.35; P &amp;lt; 0.001). The glucagon\/insulin ratio also correlated and with beta-cell function during OGTT at 60 and 120 minutes (r = \u22120.47; P &amp;lt; 0.001 and r = \u22120.32; P &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Insulin-mediated suppression of glucagon secretion in obese subjects is impaired with increasing severity of glucose intolerance and parallels the severity of insulin resistance and beta-cell dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgab019","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:03:45Z","timestamp":1612310625000},"page":"1398-1409","source":"Crossref","is-referenced-by-count":32,"title":["Impaired Suppression of Glucagon in Obese Subjects Parallels Decline in Insulin Sensitivity and Beta-Cell Function"],"prefix":"10.1210","volume":"106","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine, Diabetes Division, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes Division, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes Division, University of Texas Health Science Center, San Antonio, TX, USA"},{"name":"Audie L Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2797-0659","authenticated-orcid":false,"given":"Devjit","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes Division, University of Texas Health Science Center, San Antonio, TX, USA"},{"name":"Audie L Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"issue":"4","key":"2021122204524617300_CIT0001","doi-asserted-by":"crossref","first-page":"E671","DOI":"10.1152\/ajpendo.00492.2002","article-title":"Glucagon and regulation of glucose metabolism","volume":"284","author":"Jiang","year":"2003","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"7914","key":"2021122204524617300_CIT0002","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/S0140-6736(75)91985-6","article-title":"Letter: glucagon in pathogenesis of diabetes","volume":"1","author":"Unger","year":"1975","journal-title":"Lancet."},{"issue":"4","key":"2021122204524617300_CIT0003","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. 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