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Am J Physiol Endocrinol Metab 277: E1142-E1149, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 6, E1142-E1149, December 1999

Insulin resistance and glucose transporter expression during the euglycemic hyperinsulinemic clamp in the lamb

Nancy L. Gelardi1,2, Robert E. Rapoza1, Joseph F. Renzulli1, and Richard M. Cowett1,2,3

1 Department of Pediatrics, Women & Infants Hospital, Brown University School of Medicine, Providence, Rhode Island 02905-2401; 2 Robert Schwartz MD Center for Metabolism and Nutrition, and the Division of Neonatology, MetroHealth Medical Center, Cleveland 44109-1998; and 3 Department of Neonatology, The Children's Hospital, Cleveland Clinic Foundation, Cleveland, Ohio 44195-0001

Three- to six-day-old lambs infused with 100 mU · kg-1 · min-1 insulin required greater amounts of glucose to maintain euglycemia during a euglycemic hyperinsulinemic clamp compared with 31- to 35-day-old insulin-infused lambs (15.87 ± 3.47 vs. 4.30 ± 1.11 mg · kg-1 · min-1, P < 0.05, respectively). Endogenous glucose production persisted in both groups; however, the percent decrease compared with age-matched lambs receiving no insulin was greater in the younger group compared with the older group (53%, P < 0.001, vs. 34%, P < 0.01). The younger animals showed greater glucose utilization compared with the older animals (215 vs. 96%, respectively, P < 0.01). No effect of insulin was noted on GLUT-4 protein expression in either group. GLUT-2 expression was increased in older vs. younger lambs. Older insulin-infused lambs showed lower GLUT-2 expression than older 0 insulin-infused lambs [0.94 ± 0.07 vs. 1.64 ± 0.10 (OD) units, P < 0.005]. Increased sensitivity to insulin in the younger animals was not related to acute changes in GLUT-4 expression. Increased GLUT-2 expression with age, as well as decreased expression with hyperinsulinemia, is consistent with the development of an insulin-resistant state in the adult.

neonatal glucose homeostasis


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