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

• Published in: American journal of physiology: endocrinology and metabolism 1999-12, Vol.277 (6), p.E1142
• Main Authors: Gelardi, Nancy L, Rapoza, Robert E, Renzulli, Joseph F, Cowett, Richard M
• Format: Article
• Language: English
• ISSN: 1522-1555
• DOI: 10.1152/ajpendo.1999.277.6.E1142

Three- to six-day-old lambs infused with 100 mU ⋅ kg ⋅ min 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 ⋅ min , 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.