{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:20:45Z","timestamp":1773490845997,"version":"3.50.1"},"reference-count":76,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p>Accumulation of intracellular lipid may contribute to defective insulin secretion in type 2 diabetes. Although Zucker diabetic fatty (ZDF; fa\/fa) rat islets are fat-laden and overexpress the lipogenic master gene, sterol regulatory element binding protein 1c (SREBP-1c), the contribution of SREBP-1c to the secretory defects observed in this model remains unclear. Here we compare the gene expression profile of lean control ( fa\/+) and ZDF rat islets in the absence or presence of dominant-negative SREBP-1c (SREBP-1c DN). ZDF islets displayed elevated basal insulin secretion at 3 mmol\/l glucose but a severely depressed response to 17 mmol\/l glucose. While SREBP-1c DN reduced basal insulin secretion from ZDF islets, glucose-stimulated insulin secretion was not improved. Of 57 genes differentially regulated in ZDF islets and implicated in glucose metabolism, vesicle trafficking, ion fluxes, and\/or exocytosis, 21 were upregulated and 5 were suppressed by SREBP-1c DN. Genes underrepresented in ZDF islets were either unaffected ( Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca<jats:sup>2+<\/jats:sup>channel subunit \u03b11D, CPT2, SUR2, rab9, syt13), or inhibited ( syntaxin 7, secretogranin-2) by SREBP-1c inhibition. Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1\u03b1 (HNF1\u03b1), HNF3\u03b2\/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets. We conclude that upregulation of SREBP-1c and mild increases in triglyceride content do not explain defective glucose-stimulated insulin secretion from ZDF rats. However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model.<\/jats:p>","DOI":"10.1152\/ajpendo.00067.2006","type":"journal-article","created":{"date-parts":[[2006,6,14]],"date-time":"2006-06-14T03:34:12Z","timestamp":1150256052000},"page":"E982-E994","source":"Crossref","is-referenced-by-count":44,"title":["Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis"],"prefix":"10.1152","volume":"291","author":[{"given":"Laura E.","family":"Parton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"McMillen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingnian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Docherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Diraison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia P.","family":"Briscoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy A.","family":"Rutter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601008"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530175"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00144-1"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.8.2536"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1627-9"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75964-4"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401167200"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"R9","unstructured":"Carter D, Dillon DC, Reynolds LD, Retter MW, Fanger G, Molesh DA, Sleath PR, McNeill PD, Vedvick TS, Reed SG, Persing DH, and Houghton RL.Serum antibodies to lipophilin B detected in late stage breast cancer patients.Clin Cancer Res9: 749\u2013754, 2003."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.5.997"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-173-41611"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.8.1771"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.269003"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.2.299S"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1300-8"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.727"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S84"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031277"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2018"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.5.3760"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198705000-00024"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1038\/ng1732"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.027"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Halling DB, Aracena-Parks P, and Hamilton SL.Regulation of voltage-gated Ca2+channels by calmodulin.Sci STKE315: re15, 2005.","DOI":"10.1126\/stke.3152005re15"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.9.2503"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2509"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.12.008"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11513"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5633"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Holz RW, Brondyk WH, Senter RA, Kuizon L, and Macara IG.Evidence for the involvement of Rab3A in Ca(2+)-dependent exocytosis from adrenal chromaffin cells.J Biol Chem269: 10229\u201310234, 1994.","DOI":"10.1016\/S0021-9258(17)34051-6"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1534923100"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.10.1681"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01179"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9833"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1126\/science.2237405"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.15.8536"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.5.2582"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.10878"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80159-R"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-004-0692-9"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00093.2003"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06109.x"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.6.7750463"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102168499"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1247\/csf.20.415"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00016.2004"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-18"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.3.273"},{"key":"R49","doi-asserted-by":"crossref","unstructured":"Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, and Corkey BE.Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion.J Biol Chem267: 5802\u20135810, 1992.","DOI":"10.1016\/S0021-9258(18)42624-5"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1789"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.270.1.E133"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1541-1"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2005.05.005"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg389"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1368-9"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119534"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.5.2498"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119746"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1038\/216173a0"},{"key":"R60","unstructured":"Stiernet P, Guioit Y, Gilon P, and Henquin JC.A role of granular pH in insulin secretion (Abstract).Diabetologia48: A173, 2005."},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.2.492"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.12.1447"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.8.4753"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307800200"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1577"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00176-3"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.2007.S118"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111037200"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02513"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212488200"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201635200"},{"key":"R72","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909008199"},{"key":"R73","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04464.x"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1038\/384458a0"},{"key":"R75","doi-asserted-by":"publisher","DOI":"10.1038\/384455a0"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1602"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00067.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T09:02:42Z","timestamp":1627462962000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00067.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11]]},"references-count":76,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1152\/ajpendo.00067.2006"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00067.2006","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11]]}}}