Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats.
Hyperglycemia and compromised beta-cell development were demonstrated in neonatal rats programmed with a gestational high-fat diet. The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. Fetuses were maintained, via maternal nutrition, on either a standard laboratory diet (control) or a high-fat diet throughout gestation (HFG). Pancreata from 1-day-old neonates were excised for islet isolation and the subsequent measurement of insulin release at 2.8, 6.5, 13, and 22 mmol/L glucose. Other pancreata were either snap frozen for quantitative polymerase chain reaction or formalin fixed for immunohistochemistry followed by image analysis. The HFG neonates had reduced insulin release at 13- and 22-mmol/L glucose concentrations. No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity.
Cerf
Marlon E
ME
Diabetes Discovery Platform, Medical Research Council, Tygerberg, Cape Town, South Africa. marlon.cerf@mrc.ac.za
Chapman
Charna S
CS
Muller
Christo J
CJ
Louw
Johan
J
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D005941:Glucokinase / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism*; D006943:Hyperglycemia / Q000097:blood; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*
D004041:Dietary Fats; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; C495683:Slc2a2 protein, rat; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005941:Glucokinase