{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:35:02Z","timestamp":1761896102670},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,6,22]],"date-time":"2015-06-22T00:00:00Z","timestamp":1434931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NIAID","award":["1R01AI101041"],"award-info":[{"award-number":["1R01AI101041"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A gradual decline in insulin response is known to precede the onset of type 1 diabetes (T1D). To track age\u2010related changes in the \u03b2\u2010cell function of nonobese diabetic (NOD) mice, the most commonly used animal model for T1D, and to establish differences between those who do and do not become hyperglycemic, we performed a long\u2010term longitudinal oral glucose tolerance test (OGTT) study (10\u201342 weeks) in combination with immunofluorescence imaging of islet morphology and cell proliferation. We observed a clear biphasic decline in insulin secretion (AUC<jats:sub>0\u201330 min<\/jats:sub>) even in euglycemic animals. A first phase (10\u201328 weeks) consisted of a relatively rapid decline and paralleled diabetes development in the same cohort of animals. This was followed by a second phase (29\u201342 weeks) during which insulin secretion declined much slower while no additional animals became diabetic. Blood glucose profiles showed a corresponding, but less pronounced change: the area under the concentration curve (AUC<jats:sub>0\u2013150 min<\/jats:sub>) increased with age, and fit with a bilinear model indicated a rate\u2010change in the trendline around 28 weeks. In control NOD scids, no such changes were observed. Islet morphology also changed with age as islets become surrounded by mononuclear infiltrates, and, in all mice, islets with immune cell infiltration around them showed increased \u03b2\u2010cell proliferation. In conclusion, insulin secretion declines in a biphasic manner in all NOD mice. This trend, as well as increased \u03b2\u2010cell proliferation, is present even in the NODs that never become diabetic, whereas, it is absent in control NOD scid mice. \u00a9 2015 IUBMB Life, 67(8):634\u2013644, 2015<\/jats:p>","DOI":"10.1002\/iub.1391","type":"journal-article","created":{"date-parts":[[2015,6,22]],"date-time":"2015-06-22T10:46:51Z","timestamp":1434970011000},"page":"634-644","source":"Crossref","is-referenced-by-count":6,"title":["Biphasic decline of \u03b2\u2010cell function with age in euglycemic nonobese diabetic mice parallels diabetes onset"],"prefix":"10.1002","volume":"67","author":[{"given":"Sirlene R.","family":"Cechin","sequence":"first","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami  FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Lopez\u2010Ocejo","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami  FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darla","family":"Karpinsky\u2010Semper","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami  FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Buchwald","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami  FL USA"},{"name":"Molecular and Cellular Pharmacology Miller School of Medicine, University of Miami  FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05415-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68341-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08933"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1423"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2010"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1330"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80392-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115643"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1502"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.08.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.236"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.013"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1114"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12085"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.237"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1400"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057784"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00939.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0373"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.5.989"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(92)90039-T"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/laban1005-39"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S215"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90617.2008"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2006.08.013"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.059717"},{"key":"e_1_2_7_30_1","first-page":"A426.","article-title":"Long\u2010term reversal of hyperglycemia in experimental type 1 diabetes in NOD mice by inhibition of Smad7 with an antisense oligonucleotide","volume":"63","author":"Cechin S. 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