Hepatic and muscle insulin action during late pregnancy in the dog

Departments of 1 Molecular Physiology and Biophysics and 2 Obstetrics and Gynecology, 3 Diabetes Research and Training Center, and 4 Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee Submitted 2 June 2006 ; accepted in final form 8 September 2006 We evaluated the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester) conscious dogs ( n = 9 each) using tracer and arteriovenous difference techniques during a hyperinsulinemic euglycemic clamp. Insulin was initially (–150 to 0 min) infused intraportally at a basal rate. During 0–120 min (Low Insulin), the rate was increased by 0.2 mU·kg –1 ·min –1 , and from 120 to 240 min (High Insulin) insulin was infused at 1.5 mU·kg –1 ·min –1 . Insulin concentrations were significantly higher in NP than P during all periods. Matched subsets ( n = 5 NP and 6 P) were identified. In the subsets, insulin was 7 ± 1, 9 ± 1, and 28 ± 3 µU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5 ± 1, 7 ± 1, and 27 ± 3 µU/ml in P. Net hepatic glucose output was suppressed similarly in both subsets ( 50% with Low Insulin, 100% with High Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP dogs required more glucose (10.8 ± 1.5 vs. 6.2 ± 1.0 mg·kg –1 ·min –1 , P < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be greater in NP than P (18.6 ± 2.5 mg/min vs. 13.6 ± 2.0 mg/min, P = 0.06). The normal canine liver remains insulin sensitive during late pregnancy. Differing insulin concentrations in pregnant and nonpregnant women and excessive insulin infusion rates may explain previous findings of hepatic insulin resistance in healthy pregnant women. insulin resistance; skeletal muscle; liver; hyperinsulinemic euglycemic clamp Address for reprint requests and other correspondence: Mary Courtney Moore, 702 Light Hall, Dept. of Molecular Physiology and Biophysics, Vanderbilt Univ. School of Medicine, Nashville, TN 37232 (e-mail: genie.moore{at}vanderbilt.edu )