Relationship between decrements in glucose level and metabolic response to hypoglycemia in absence of counterregulatory hormones in the conscious dog.
To determine the relationship between decreases in glucose and metabolic regulation in the absence of counterregulatory hormones, we infused overnight-fasted, conscious, adrenalectomized dogs (lacking cortisol and EPI) with somatostatin (to eliminate glucagon and growth hormone) and intraportal insulin (30 pmol.kg-1.min-1), creating arterial insulin levels of approximately 2000 pM. Glucose was infused during one 120-min period, two 90-min periods, and one 45-min period to establish levels of 5.9 +/- 0.1, 3.4 +/- 0.1, 2.5 +/- 0.1, and 1.7 +/- 0.1 mM, respectively. NE levels were 1.24 +/- 0.23, 1.85 +/- 0.27, 2.04 +/- 0.26, and 2.50 +/- 0.20 nM, respectively. During the euglycemic control period, the liver took up glucose (7.5 +/- 1.9 mumol.kg-1.min-1), but hypoglycemia triggered successively greater rates of net hepatic glucose output (3.0 +/- 0.7, 4.6 +/- 0.9, and 6.9 +/- 1.4 mumol.kg-1.min-1). Total gluconeogenic precursor uptake by the liver increased with hypoglycemia. Intrahepatic gluconeogenic efficiency rose progressively (by 106 +/- 42, 199 +/- 56, and 268 +/- 55%). Both glycerol and NEFA levels rose, indicating lipolysis was enhanced. Net hepatic NEFA uptake and ketone production increased proportionally, but the ketone level rose only with severe hypoglycemia. In conclusion, despite marked hyperinsulinemia and the absence of glucagon, EPI, and cortisol, we observed that lipolysis and glucose and ketone production increase in response to decreases in glucose. This suggests that neural and/or autoregulatory mechanisms can play a role in combating hypoglycemia.
Connolly
C C
CC
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Adkins-Marshall
B A
BA
Neal
D W
DW
Pugh
W
W
Jaspan
J B
JB
Cherrington
A D
AD
D000315:Adrenalectomy; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood*; D005943:Gluconeogenesis; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006854:Hydrocortisone / Q000097:blood*; D007003:Hypoglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood* / Q000494:pharmacology*; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D007773:Lactates; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine