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1 Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
2 Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
3 Nashville, Tennessee, United States; Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
4 Diabetes Research & Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
5 Diabetes Research & Training Center and Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
6 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville,, Tennessee, United States
* To whom correspondence should be addressed. E-mail: genie.moore{at}vanderbilt.edu.
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 120-240 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 Ra. 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.
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