{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:26:02Z","timestamp":1792005962436,"version":"4.4.0"},"reference-count":44,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":4568,"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":[[2009,4,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Obesity is a known risk factor for type 2 diabetes. However, most obese individuals do not develop diabetes because they adapt to insulin resistance by increasing \u03b2-cell mass and insulin secretion. Islet pathology in type 2 diabetes is characterized by \u03b2-cell loss, islet amyloid derived from islet amyloid polypeptide (IAPP), and increased \u03b2-cell apoptosis characterized by endoplasmic reticulum (ER) stress. We hypothesized that IAPP-induced ER stress distinguishes successful versus unsuccessful islet adaptation to insulin resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>To address this, we fed wild-type (WT) and human IAPP transgenic (HIP) rats either 10 weeks of regular chow or a high-fat diet and prospectively examined the relations among \u03b2-cell mass and turnover, \u03b2-cell ER stress, insulin secretion, and insulin sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>A high-fat diet led to comparable insulin resistance in WT and HIP rats. WT rats compensated with increased insulin secretion and \u03b2-cell mass. In HIP rats, in contrast, neither \u03b2-cell function nor mass compensated for the increased insulin demand, leading to diabetes. The failure to increase \u03b2-cell mass in HIP rats was the result of ER stress\u2013induced \u03b2-cell apoptosis that increased in proportion to diet-induced insulin resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>IAPP-induced ER stress distinguishes the successful versus unsuccessful islet adaptation to a high-fat diet in rats. These studies are consistent with the hypothesis that IAPP oligomers contribute to increased \u03b2-cell apoptosis and \u03b2-cell failure in humans with type 2 diabetes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db08-1464","type":"journal-article","created":{"date-parts":[[2009,1,17]],"date-time":"2009-01-17T02:47:32Z","timestamp":1232160452000},"page":"906-916","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":84,"title":["Successful Versus Failed Adaptation to High-Fat Diet\u2013Induced Insulin Resistance"],"prefix":"10.2337","volume":"58","author":[{"given":"Aleksey V.","family":"Matveyenko","sequence":"first","affiliation":[{"name":"From the Larry Hillblom Islet Research Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Gurlo","sequence":"additional","affiliation":[{"name":"From the Larry Hillblom Islet Research Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Daval","sequence":"additional","affiliation":[{"name":"From the Larry Hillblom Islet Research Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"From the Larry Hillblom Islet Research Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Butler","sequence":"additional","affiliation":[{"name":"From the Larry Hillblom Islet Research Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2009,1,16]]},"reference":[{"key":"2022051622391882300_B1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2337\/diab.45.5.633","article-title":"Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM","volume":"45","author":"Carey","year":"1996","journal-title":"Diabetes"},{"key":"2022051622391882300_B2","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1007\/BF00400597","article-title":"Role of insulin resistance in the pathogenesis of NIDDM","volume":"38","author":"Yki-Jarvinen","year":"1995","journal-title":"Diabetologia"},{"key":"2022051622391882300_B3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.2337\/diacare.15.3.318","article-title":"Pathogenesis of NIDDM. 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