{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T19:41:26Z","timestamp":1776886886339,"version":"3.51.2"},"reference-count":18,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3575,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the \u03b2-cell could cause \u03b2-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate \u03b2-cell function in subjects with normal glucose tolerance (NGT) and whether they contribute to dysglycemia in impaired glucose regulation (IGR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Insulin sensitivity (by euglycemic clamp), insulin-induced secretory response at isoglycemia (IISR) (as C-peptide percent change from basal during the clamp), glucose-induced secretory response (GISR) to an intravenous glucose bolus, and \u03b2-cell glucose sensitivity (\u03b2-GS) (by oral glucose tolerance test [OGTT] modeling) were measured in 1,151 NGT and 163 IGR subjects from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>In NGT, IISR was related to both insulin sensitivity and antecedent insulin exposure; GISR was related to insulin exposure. IISR was positively, if weakly, related to \u03b2-GS (r= 0.16, P &amp;lt; 0.0001). Both IISR (\u221223 [39] vs. \u22129 [2]%, median [interquartile range], P &amp;lt; 0.03) and \u03b2-GS (69 [47] vs. 118 [83] pmol \u22c5 min\u20131 \u22c5 m\u20132 \u22c5 mmol\u20131 \u22c5 L, P &amp;lt; 0.0001) were decreased in IGR compared with NGT. Insulin sensitivity and \u03b2-GS were the major determinants of mean OGTT glucose in both NGT and IGR, with a minor role for IISR. In a multivariate logistic model, IGR was predicted by \u03b2-GS (odds ratio 4.84 [95% CI 2.89\u20138.09]) and insulin sensitivity (3.06 [2.19\u20134.27]) but not by IISR (1.11 [0.77\u20131.61]).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Pre-exposure to physiological hyperinsulinemia stimulates insulin secretion to a degree that depends on insulin sensitivity. However, this phenomenon has limited impact on \u03b2-cell dysfunction and dysglycemia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db11-0827","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T23:12:36Z","timestamp":1319584356000},"page":"3141-3147","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":47,"title":["Influence of Hyperinsulinemia and Insulin Resistance on In Vivo \u03b2-Cell Function"],"prefix":"10.2337","volume":"60","author":[{"given":"Andrea","family":"Mari","sequence":"first","affiliation":[{"name":"National Research Council Institute of Biomedical Engineering, Padova, Italy"}]},{"given":"Andrea","family":"Tura","sequence":"additional","affiliation":[{"name":"National Research Council Institute of Biomedical Engineering, Padova, Italy"}]},{"given":"Andrea","family":"Natali","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Pisa, Pisa, Italy"}]},{"given":"Christian","family":"Anderwald","sequence":"additional","affiliation":[{"name":"National Research Council Institute of Biomedical Engineering, Padova, Italy"},{"name":"Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria"}]},{"given":"Beverley","family":"Balkau","sequence":"additional","affiliation":[{"name":"INSERM U258, Villejuif, France"}]},{"given":"Nebojsa","family":"Lalic","sequence":"additional","affiliation":[{"name":"Clinical Center of Serbia, Institute for Endocrinology, Diabetes and Metabolic Diseases, Belgrade, Serbia"}]},{"given":"Mark","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, U.K."}]},{"given":"Ele","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Pisa, Pisa, Italy"}]},{"name":"for the RISC Investigators","sequence":"additional","affiliation":[]}],"member":"1167","published-online":{"date-parts":[[2011,11,13]]},"reference":[{"key":"2022031209374806300_B1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1146\/annurev.physiol.65.092101.142540","article-title":"Insulin receptor knockout mice","volume":"65","author":"Kitamura","year":"2003","journal-title":"Annu Rev Physiol"},{"key":"2022031209374806300_B2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev.nutr.28.061807.155530","article-title":"Insulin signaling in the pancreatic beta-cell","volume":"28","author":"Leibiger","year":"2008","journal-title":"Annu Rev Nutr"},{"key":"2022031209374806300_B3","doi-asserted-by":"crossref","first-page":"4770","DOI":"10.1073\/pnas.1000002107","article-title":"Insulin enhances glucose-stimulated insulin secretion in healthy humans","volume":"107","author":"Bouche","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031209374806300_B4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00125-002-1009-0","article-title":"The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes","volume":"46","author":"Kahn","year":"2003","journal-title":"Diabetologia"},{"key":"2022031209374806300_B5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1210\/jc.2004-1133","article-title":"Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis","volume":"90","author":"Ferrannini","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031209374806300_B6","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00125-009-1647-6","article-title":"Impaired beta cell glucose sensitivity rather than inadequate compensation for insulin resistance is the dominant defect in glucose intolerance","volume":"53","author":"Mari","year":"2010","journal-title":"Diabetologia"},{"key":"2022031209374806300_B7","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s00125-004-1335-5","article-title":"The EGIR-RISC STUDY (The European group for the study of insulin resistance: relationship between insulin sensitivity and cardiovascular disease risk): I. 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