Interaction of free fatty acids and epinephrine in regulating hepatic glucose production in conscious dogs.
To determine the effects of an increase in lipolysis on the glycogenolytic effect of epinephrine (EPI), the catecholamine was infused portally into 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence [portal (Po)-EPI+FFA, n = 6] and absence (Po-EPI+SAL, n = 6) of peripheral Intralipid infusion. Control groups with high glucose (70% increase) and free fatty acid (FFA; 200% increase; HG+FFA, n = 6) and high glucose alone (HG+SAL, n = 6) were also included. Hepatic sinusoidal EPI levels were elevated (Delta 568 +/- 77 and Delta 527 +/- 37 pg/ml, respectively) in Po-EPI+SAL and EPI+FFA but remained basal in HG+FFA and HG+SAL. Arterial plasma FFA increased from 613 +/- 73 to 1,633 +/- 101 and 746 +/- 112 to 1,898 +/- 237 micromol/l in Po-EPI+FFA and HG+FFA but did not change in EPI+SAL or HG+SAL. Net hepatic glycogenolysis increased from 1.5 +/- 0.3 to 3.1 +/- 0.4 mg x kg(-1) x min(-1) (P < 0.05) by 30 min in response to portal EPI but did not rise (1.8 +/- 0.2 to 2.1 +/- 0.3 mg x kg(-1) x min(-1)) in response to Po-EPI+FFA. Net hepatic glycogenolysis decreased from 1.7 +/- 0.2 to 0.9 +/- 0.2 and 1.6 +/- 0.2 to 0.7 +/- 0.2 mg x kg(-1) x min(-1) by 30 min in HG+FFA and HG+SAL. Hepatic gluconeogenic flux to glucose 6-phosphate increased from 0.6 +/- 0.1 to 1.2 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; by 3 h) and 0.7 +/- 0.1 to 1.6 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; at 90 min) in HG+FFA and Po-EPI+FFA. The gluconeogenic parameters remained unchanged in the Po-EPI+SAL and HG+SAL groups. In conclusion, increased FFA markedly changed the mechanism by which EPI stimulated hepatic glucose production, suggesting that its overall lipolytic effect may be important in determining its effect on the liver.
Chu
Chang An
CA
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Galassetti
Pietro
P
Igawa
Kayano
K
Sindelar
Dana K
DK
Neal
Doss W
DW
Burish
Mark
M
Cherrington
Alan D
AD
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000096:biosynthesis*; D001794:Blood Pressure; D003243:Consciousness; D004285:Dogs; D004837:Epinephrine / Q000097:blood* / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000502:physiology; D005990:Glycerol / Q000378:metabolism; D006339:Heart Rate; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D009638:Norepinephrine / Q000097:blood; D013566:Sympathomimetics / Q000097:blood* / Q000494:pharmacology
D000596:Amino Acids; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013566:Sympathomimetics; D019344:Lactic Acid; D005934:Glucagon; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine