Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog.
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 (Delta3.01 +/- 0.46 and Delta1.31 +/- 0.13 nmol/l, P < 0.05). Net hepatic glucose output (NHGO; micromol.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 micromol.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 micromol.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.
Connolly
Cynthia C
CC
Department of Molecular Physiology and Biophysics, and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Aglione
Lisa N
LN
Smith
Marta S
MS
Lacy
D Brooks
DB
Moore
Mary Courtney
MC
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006728:Hormones / Q000097:blood*; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000378:metabolism; D007700:Kinetics; D008102:Liver Circulation; D009994:Osmolar Concentration; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000503:physiopathology*; D011270:Pregnancy, Animal; D011374:Progesterone / Q000097:blood; D011498:Protein Precursors / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D007657:Ketone Bodies; D011498:Protein Precursors; D011374:Progesterone; D006003:Glycogen; D005947:Glucose