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At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by \u223c43% and \u223c6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased \u03b2-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and\/or cortisol-induced accelerated fetal \u03b2-cell maturation and may contribute to premature \u03b2-cell function loss and predisposition to obesity and metabolic disease in offspring.<\/jats:p>","DOI":"10.1152\/ajpregu.00072.2009","type":"journal-article","created":{"date-parts":[[2009,7,16]],"date-time":"2009-07-16T02:10:53Z","timestamp":1247710253000},"page":"R835-R843","source":"Crossref","is-referenced-by-count":152,"title":["Maternal obesity accelerates fetal pancreatic \u03b2-cell but not \u03b1-cell development in sheep: prenatal consequences"],"prefix":"10.1152","volume":"297","author":[{"given":"Stephen P.","family":"Ford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrna M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek T.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret W.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Nathanielsz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Nijland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R, Lane RH.Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome.J Mol Endocrinol41: 91\u2013102, 2004."},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1159\/000014000"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.157818"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.072009"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.079756"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1808"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Breant B, Gesina E, Blondeau B.Nutrition, glucocorticoids and pancreas development.Horm Res65,Suppl3: 98\u2013104, 2006.","DOI":"10.1159\/000091513"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Callaway LK, Prins JB, Chang AM, McIntyre HD.The prevalence and impact of overweight and obesity in an Australian obstetric population.Med J Aust184: 56\u201359, 2006.","DOI":"10.5694\/j.1326-5377.2006.tb00115.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.271.5.E865"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(03)00828-7"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080393"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1079\/PNS19950003"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1071\/RD9950351"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1984.sp002808"},{"key":"R17","unstructured":"Fowden AL, Forhead AJ.The role of hormones in intrauterine development. 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