Insulin resistance and glucose transporter expression during the euglycemic hyperinsulinemic clamp in the lamb.
Three- to six-day-old lambs infused with 100 mU x kg(-1) x 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 x kg(-1) x 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.
Gelardi
N L
NL
Department of Pediatrics, Women & Infants Hospital, Brown University School of Medicine, Providence, Rhode Island 02905-2401, USA.
Rapoza
R E
RE
Renzulli
J F
JF
Cowett
R M
RM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D006339:Heart Rate; D006706:Homeostasis / Q000502:physiology; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep
D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D006854:Hydrocortisone