| Title: | Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction |
| Author(s): | Camacho LE; Chen X; Hay WW; Limesand SW; |
| Address: | "School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona. Chongqing Key Laboratory of Forage & Herbivore, College of Animal Science and Technology, Southwest University, Chongqing, China; and. Perinatal Research Center, University of Colorado School of Medicine, Aurora, Colorado. School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona; limesand@email.arizona.edu" |
| Journal Title: | Am J Physiol Regul Integr Comp Physiol |
| DOI: | 10.1152/ajpregu.00068.2017 |
| ISSN/ISBN: | 1522-1490 (Electronic) 0363-6119 (Print) 0363-6119 (Linking) |
| Abstract: | "Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR (n = 7) were compared with control lambs (n = 8). GSIS was measured at 8 +/- 1 days of age, and at 15 +/- 1 days, body weight-specific glucose utilization rates were measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less (P < 0.05) than controls at birth. Fasting plasma glucose and insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared with controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and beta-cell mass were not different, indicating that IUGR beta-cells have an intrinsic enhancement in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared with controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants" |
| Keywords: | "Animals Animals, Newborn Blood Glucose/*metabolism Female Fetal Growth Retardation/*etiology/*physiopathology Insulin/*metabolism *Insulin Resistance Insulin Secretion Male Placental Insufficiency/*physiopathology Pregnancy Sheep glucose insulin sensitivi;" |
| Notes: | "MedlineCamacho, Leticia E Chen, Xiaochuan Hay, William W Jr Limesand, Sean W eng K12 HD068372/HD/NICHD NIH HHS/ R01 DK084842/DK/NIDDK NIH HHS/ T32 HD007186/HD/NICHD NIH HHS/ 2017/05/12 Am J Physiol Regul Integr Comp Physiol. 2017 Aug 1; 313(2):R101-R109. doi: 10.1152/ajpregu.00068.2017. Epub 2017 May 10" |
