Insulin action during late pregnancy in the conscious dog.
Our aim was to assess the magnitude of peripheral insulin resistance and whether changes in hepatic insulin action were evident in a canine model of late (3rd trimester) pregnancy. A 3-h hyperinsulinemic (5 mU.kg(-1).min(-1)) euglycemic clamp was conducted using conscious, 18-h-fasted pregnant (P; n = 6) and nonpregnant (NP; n = 6) female dogs in which catheters for intraportal insulin infusion and assessment of hepatic substrate balances were implanted approximately 17 days before experimentation. Arterial plasma insulin rose from 11 +/- 2 to 192 +/- 24 and 4 +/- 2 to 178 +/- 5 microU/ml in the 3rd h in NP and P, respectively. Glucagon fell equivalently in both groups. Basal net hepatic glucose output was lower in NP (1.9 +/- 0.1 vs. 2.4 +/- 0.2 mg.kg(-1).min(-1), P < 0.05). Hyperinsulinemia completely suppressed hepatic glucose release in both groups (-0.4 +/- 0.2 and -0.1 +/- 0.2 mg.kg(-1).min(-1) in NP and P, respectively). More exogenous glucose was required to maintain euglycemia in NP (15.2 +/- 1.3 vs. 11.5 +/- 1.1 mg.kg(-1).min(-1), P < 0.05). Nonesterified fatty acids fell similarly in both groups. Net hepatic gluconeogenic amino acid uptake with high insulin did not differ in NP and P. Peripheral insulin action is markedly impaired in this canine model of pregnancy, whereas hepatic glucose production is completely suppressed by high circulating insulin levels.
Connolly
Cynthia C
CC
Department of Molecular Physiology and Biophysics, Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Aglione
Lisa N
LN
Smith
Marta S
MS
Lacy
D Brooks
DB
Moore
Mary Courtney
MC
D000409:Alanine / Q000097:blood; D000596:Amino Acids / Q000097:blood; D000818:Animals; D003243:Consciousness; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D007659:Ketones / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008102:Liver Circulation; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*
D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007659:Ketones; D019344:Lactic Acid; D005947:Glucose; D000409:Alanine; D005990:Glycerol