Glucose Inhibition of Epinephrine Stimulation of Hepatic Gluconeogenesis by Blockade of the α-Receptor Function

Publisher Website
Google Scholar
Abstract
For isolated rat hepatocytes, glucagon, 3'':5''-cyclic[c]AMP, cGMP and epinephrine stimulated the rate of gluconeogenesis from substrates not involving pathways of mitochondrial metabolism. From estimation of the rates of glucose formation, fructose 6-phosphate phosphorylation and lactate and pyruvate formation, epinephrine and cGMP stimulated gluconeogenesis from either galactose or fructose by influencing the rate of reactions involving fructose 6-phosphate in a manner similar to that reported for glucagon and cAMP. Each agent inhibited flux through phosphofructokinase (EC 2.7.1.11) and enhanced flux through fructose diphosphatase (EC 3.1.3.11), resulting in the re-direction of carbon from lactate and pyruvate formation to glucose synthesis. In addition to cGMP, dibutyryl 3'':5''-cyclic GMP, 8-bromo 3'':5''-cyclic GMP, 8-benzyl-thio 3'':5''-cyclic GMP and 8-(4-chlorophenyl)thio 3'':5''-cyclic GMP stimulated glucose formation and inhibited lactate and pyruvate formation from galactose. Guanosine monophosphate and 2'':3''-cyclic GMP are inactive. As the stimulatory effect of epinephrine is inhibited by phenoxybenzamine and not by propranolol, and is not stimulated by isoproterenol, catecholamine activity probably is expressed through the .alpha.-receptor. Increased extracellular glucose concentration (> 10 mM) decreased the stimulatory effect of epinephrine, cGMP, and partially that of cAMP but did not alter glucagon efficacy.