{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:55:40Z","timestamp":1788825340039,"version":"build-2803163510"},"reference-count":35,"publisher":"The Endocrine Society","issue":"7","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK80157"],"award-info":[{"award-number":["R01-DK80157"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK089229"],"award-info":[{"award-number":["R01-DK089229"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CTSA","award":["UL1TR000149"],"award-info":[{"award-number":["UL1TR000149"]}]},{"name":"San Antonio Claude D. Pepper Older Americans Independence Center","award":["AG044271"],"award-info":[{"award-number":["AG044271"]}]},{"name":"San Antonio Nathan Shock Center","award":["AG013319"],"award-info":[{"award-number":["AG013319"]}]},{"name":"NovoNordisk Foundation"},{"name":"Italian Ministry of Research"},{"DOI":"10.13039\/501100004462","name":"Consiglio Nazionale delle Ricerche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004462","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with \u03b2-cell dysfunction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research Design<\/jats:title>\n                  <jats:p>A total of 40 young (25 \u00b1 3 years) and 53 older (74 \u00b1 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of \u03b2-cell glucose sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Matsuda index, early phase ISR (0 to 30 minutes), and parameters of \u03b2-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0\u2013120 was 2.8 \u00b1 0.1 in Y-NGT, 3.8 \u00b1 0.5 in O-NGT, and 3.7 \u00b1 0.4 nmol\/L\u2219120 minutes in O-IGT subjects; P &lt; 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0\u2013120 was 4.7 \u00b1 0.3 in Y-NGT, 6.0 \u00b1 0.4 in O-NGT, and 4.8 \u00b1 0.3 nmol\/L\u2219120 minutes in O-IGT subjects; P &lt; 0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2018-00260","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T14:04:12Z","timestamp":1523887452000},"page":"2613-2619","source":"Crossref","is-referenced-by-count":26,"title":["Older Subjects With \u03b2-Cell Dysfunction Have an Accentuated Incretin Release"],"prefix":"10.1210","volume":"103","author":[{"given":"Jos\u00e9","family":"de Jes\u00fas Garduno-Garcia","sequence":"first","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"},{"name":"Texas Diabetes Institute, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"},{"name":"Institute of Clinical Physiology, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"},{"name":"Texas Diabetes Institute, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raweewan","family":"Lertwattanarak","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"},{"name":"Texas Diabetes Institute, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"},{"name":"San Antonio Geriatric Research, Education and Clinical Center, San Antonio, Texas"},{"name":"Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"2019081407050298900_B1","doi-asserted-by":"crossref","first-page":"5S27","DOI":"10.1016\/S1262-3636(05)73649-1","article-title":"Diabetes mellitus in the elderly: insulin resistance and\/or impaired insulin secretion","volume":"31","author":"Scheen","year":"2005","journal-title":"Diabetes Metab"},{"issue":"6","key":"2019081407050298900_B2","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2337\/diabetes.52.6.1475","article-title":"The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging","volume":"52","author":"Meigs","year":"2003","journal-title":"Diabetes"},{"issue":"12","key":"2019081407050298900_B3","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.2337\/dc12-1801","article-title":"Diabetes in older adults","volume":"35","author":"Kirkman","year":"2012","journal-title":"Diabetes Care"},{"issue":"7","key":"2019081407050298900_B4","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1093\/gerona\/60.7.872","article-title":"Abdominal adiposity assessed by dual energy X-ray absorptiometry provides a sex-independent predictor of insulin sensitivity in older adults","volume":"60","author":"Lee","year":"2005","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"4","key":"2019081407050298900_B5","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1089\/met.2009.0090","article-title":"Walking in old age and development of metabolic syndrome: the health, aging, and body composition 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