Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog.
The role of epinephrine and norepinephrine in contributing to the alterations in hepatic glucose metabolism during a 70-h stress hormone infusion (SHI) was investigated in four groups of chronically catheterized (20-h-fasted) conscious dogs. SHI increased glucagon (approximately 5-fold), epinephrine (approximately 10-fold), norepinephrine (approximately 10-fold), and cortisol (approximately 6-fold) levels. Dogs received either all the hormones (SHI; n = 5), all the hormones except epinephrine (SHI-Epi; n = 6), or all the hormones except norepinephrine (SHI-NE; n = 6). In addition, six dogs received saline only (Sal). Glucose production (Ra) and gluconeogenesis were assessed after a 70-h hormone or saline infusion with the use of tracer ([3-(3)H]glucose and [U-(14)C]alanine) and arteriovenous difference techniques. SHI increased glucose levels (108 +/- 2 vs. 189 +/- 10 mg/dl) and Ra (2.6 +/- 0.2 vs. 4.1 +/- 0.3 mg x kg(-1) x min(-1)) compared with Sal. The absence of an increase in epinephrine markedly attenuated these changes (glucose and Ra were 140 +/- 6 mg/dl and 2.7 +/- 0.4 mg x kg(-1) x min(-1), respectively). Only 25% of the blunted rise in Ra could be accounted for by an attenuation of the rise in net hepatic gluconeogenic precursor uptake (0.9 +/- 0.1, 1.5 +/- 0.1, and 1.1 +/- 0.2 mg x kg(-1) x min(-1) for Sal, SHI, and SHI-Epi, respectively). The absence of an increase in norepinephrine did not blunt the rise in arterial glucose levels, Ra, or net hepatic gluconeogenic precursor uptake (they rose to 195 +/- 21 mg/dl, 3.7 +/- 0.5 mg x kg(-1) x min(-1), and 1.7 +/- 0.2 mg x kg(-1) min(-1), respectively). In summary, during chronic SHI, the rise in epinephrine exerts potent stimulatory effects on glucose production principally by enhancing hepatic glycogenolysis, although the rise in circulating norepinephrine has minimal effects.
McGuinness
O P
OP
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232-0615, USA.
Shau
V
V
Benson
E M
EM
Lewis
M
M
Snowden
R T
RT
Greene
J E
JE
Neal
D W
DW
Cherrington
A D
AD
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine