Impact of acute epinephrine removal on hepatic glucose metabolism during stress hormone infusion.
We examined the effect of acute discontinuation of an epinephrine (EPI) infusion on hepatic glucose metabolism during stress hormone infusion (SHI). Glucose metabolism was assessed in 11 conscious, 20-hour fasted dogs using tracer and arteriovenous techniques after a 3-day exposure to SHI. SHI increased EPI, norepinephrine, cortisol, and glucagon levels (approximately sixfold to 10-fold), which led to marked hyperglycemia, hyperinsulinemia, and accelerated glucose metabolism. On day 3, EPI infusion was acutely discontinued for 180 minutes in five dogs while infusion of the other hormones was continued (SHI - EPI). In the remaining six dogs, all hormones were continued for the duration of the study (SHI + EPI). In SHI - EPI, EPI levels decreased from 1,678+/-191 to 161+/-47 pg/mL. Isoglycemia (183+/-10 to 185+/-15 mg/dL) was maintained with an exogenous glucose infusion. Arterial insulin levels increased from 41+/-8 to 64+/-8 microU/mL. Whole-body glucose utilization increased from 3.5+/-0.5 to 9.4+/-1.9 mg/kg/min. Nonesterified fatty acids ([NEFAs] 763+/-292 to 147+/-32 micromol/L) decreased. Net hepatic glucose output decreased (2.6+/-0.6 to 0.1+/-0.3 mg/kg/min). In SHI + EPI, hepatic glucose metabolism remained unaltered. In summary, EPI plays a pivotal role during SHI by stimulating glucose production and inhibiting glucose utilization. In part, these effects are mediated by restraining pancreatic insulin secretion.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
O P
OP
McGuinness
R T
RT
Snowden
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C
Moran
D W
DW
Neal
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Fujiwara
A D
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Cherrington
D000409:Alanine / Q000378:metabolism; D000818:Animals; D004285:Dogs; D004338:Drug Combinations; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006728:Hormones / Q000097:blood / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D013997:Time Factors
D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine