HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/E231    most recent 00222.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Dufour, S. Articles by Petersen, K. F. PubMed PubMed Citation Articles by Dufour, S. Articles by Petersen, K. F.

Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans

Departments of ¹Internal Medicine and ²Cellular and Molecular Physiology, ³Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut

Submitted 6 April 2009 ; accepted in final form 16 May 2009

The relative contributions of net hepatic glycogenolysis (NHG) and gluconeogenesis to rates of glucose production during a physiological increment in plasma epinephrine concentrations, independent of changes in plasma insulin concentrations, were determined in seven fasting, healthy young subjects. Plasma insulin concentrations were kept constant by infusing somatostatin (0.1 µg·kg^–1·min^–1) and replacing basal insulin (24 pmol·m^–2·min^–1). Epinephrine (1.2 µg·m^–2·min^–1) was infused for 90 min while NHG was assessed directly by ¹³C magnetic resonance spectroscopy. The rate of glucose production was assessed using [6,6-²H₂]glucose, and gluconeogenesis was calculated as the difference between the rate of glucose production and NHG. Plasma epinephrine concentrations increased rapidly from 100 to 2,000 pmol/l (P < 0.00001) accompanied by an increase in plasma glucose concentrations from 4.3 ± 0.2 to 13.3 ± 0.3 mmol/l at 90 min (P = 0.00001). This increase in plasma epinephrine concentration resulted in a 2.5-fold increase in glucose production (from 14.4 ± 1.0 µmol·kg^–1·min^–1 to 35.7 ± 2.0 µmol·kg^–1·min^–1, P < 0.0001), which lasted for 60 min (phase 1), after which glucose production decreased to 31.2 ± 1.9 µmol·kg^–1·min^–1 (P < 0.0001 vs. basal) during the last 30 min of the epinephrine infusion (phase 2). Hepatic glycogen concentrations decreased almost linearly during phase 1, and rates of NHG were 19.9 ± 3.0 µmol·kg^–1·min^–1 (P = 0.005 vs. basal), which could account for 60% of glucose production. During phase 2, NHG decreased to 7.3 ± 2.8 µmol·kg^–1·min^–1 (P = 0.02 vs. peak), accounting for only 20% of glucose production. In conclusion, in the presence of basal plasma insulin and glucagon concentrations, a physiological increase in plasma epinephrine concentrations stimulates glucose production with an initial, 60-min transient phase caused by stimulation of NHG and a second phase that can mostly be attributed to a twofold increase in rates of gluconeogenesis.

net hepatic glycogenolysis; gluconeogenesis; epinephrine; humans