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Am J Physiol Endocrinol Metab 287: E480-E488, 2004. First published May 4, 2004; doi:10.1152/ajpendo.00529.2003
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Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog

Cynthia C. Connolly,{dagger} Lisa N. Aglione, Marta S. Smith, D. Brooks Lacy, and Mary Courtney Moore

Department of Molecular Physiology and Biophysics, and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Submitted 20 November 2003 ; accepted in final form 30 April 2004

The impact of pregnancy on the counterregulatory response to insulin-induced hypoglycemia was examined in six nonpregnant (NP) and six pregnant (P; 3rd trimester) conscious dogs by tracer and arteriovenous difference techniques. After basal sampling, insulin was infused intraportally at 30 pmol·kg–1·min–1 for 180 min. Insulin rose from 70 ± 15 to 1,586 ± 221 pmol/l and 27 ± 4 to 1,247 ± 61 pmol/l in the 3rd h in NP and P, respectively. Arterial glucose fell from 5.9 ± 0.2 to 2.3 ± 0.2 mmol/l in P. Glucose was infused in NP to equate the rate of fall of glucose and the steady-state concentrations in the groups (5.9 ± 0.2 to 2.3 ± 0.1 mmol/l in NP). Glucagon was 32 ± 6, 69 ± 11, and 48 ± 10 ng/l (basal and 1st and 3rd h) in NP, but the response was attenuated in P (34 ± 5, 46 ± 6, 41 ± 9 ng/l). Cortisol and epinephrine rose similarly in both groups, but norepinephrine rose more in NP ({Delta}3.01 ± 0.46 and {Delta}1.31 ± 0.13 nmol/l, P < 0.05). Net hepatic glucose output (NHGO; µmol·kg–1·min–1) increased from 10.6 ± 1.8 to 21.2 ± 3.3 in NP (3rd h) but did not increase in P (15.1 ± 1.5 to 15.3 ± 2.8 µmol·kg–1·min–1, P < 0.05 between groups). The glycogenolytic contribution to NHGO in NP increased from 5.8 ± 0.7 to 10.4 ± 2.5 µmol·kg–1·min–1 by 90 min but steadily declined in P. The increase in glycerol levels and the gluconeogenic contribution to NHGO were 50% less in P than in NP, but ketogenesis did not differ. The glucagon and norepinephrine responses to insulin-induced hypoglycemia are blunted in late pregnancy in the dog, impacting on the magnitude of the metabolic responses to the fall in glucose.

gluconeogenesis; glycogenolysis; ketogenesis; hepatic glucose production



Address for reprint requests and other correspondence: M. C. 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).




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