Comparative effect of glucagon and isoproterenol on hepatic glycogenolysis and glycolysis in isolated perfused liver

Abstract

The effect of glucagon and isoproterenol (ß-adrenergic agonist) on hepatic glycogenolysis and glycolysis in isolated perfused liver was compared. The levels of isoproterenol and glucagon which promoted the maximal activation of glycogenolysis were 20 µM and 1nM respectively. However, glucagon (1 nM) not only increased glycogenolysis but also inhibited glycolysis. Because adenosine-3'-5'-cyclic monophosphate (cAMP) is a common second messenger to glucagon and isoproterenol, the level of cAMP that simulates the effect of these substances were investigated. The concentration of cAMP that inhibited glycolysis was five times higher (15 ìM) than that which stimulated glycogenolysis (3 ìM). Similar inhibition of glycolysis was obtained with cAMP agonists resistant to phosphodiesterases, i.e., 8-Br-cAMP and N 6 -monobutyryl-cAMP (6-MB-cAMP) at the concentration of 3 ìM. Thus, apparently glucagon could produce higher cellular levels of cAMP than that obtained with the activation of ß-adrenergic receptors. The higher amount of cAMP could be enough to overcome the action of phosphodiesterases and penetrate in the cytosol creating a favourable gradient to inhibit the enzymes of glycolysis.

Liver glycogen metabolism during short‐term insulin‐induced hypoglycemia in fed rats

“…Because post receptor mechanisms are important in regulating liver response to glucagon and isoprorenol in terms of glycogen catabolism, 26 we employed cyanide, a respiratory chain inhibitor, which bypasses membrane receptors to activate glycogenolysis and glycolysis. Thus, in contrast with glucagon and isoproterenol, the responsiveness of glycogen breakdown in the livers of IIH rats infused with cyanide remained unchanged.…”

“…We previously reported 26 that the effect of the infusion of glucagon and isoproterenol on activation of glycogenolysis during IIH was mediated, partly at least, by cAMP and the concentration of cAMP necessary to simulate the effect of glucagon on glycogenolysis was greater than that necessary to simulate the effects of isoproterenol. Therefore, we can suggest that the infused glucagon was capable of inducing higher intracellular concentrations of cAMP compared with isoproterenol, and for this reason glucagon was less influenced by the intensification of cAMP catabolism promoted by insulin through activation of phosphodiesterase 3B.…”

Simulating Signalling Pathways With BioWayS

“…For each reaction we specified the initial concentration c of reactants , the probability p to occur and the time t (see parameter t in Equation (2)) between two subsequent events of product formation. These parameters were estimated accordingly to literature data [5,22,23,27,34]. In particular t is estimated A reaction pathway for the glycogen breakdown (taken from [5] and https://files.nyu.edu/gcl1/public/).…”

“…For each mode of simulation, we use the lower, medium and upper limit of the molar concentration of the variables: InfLim, MedLim, MaxLim, respectively. Adapted from [5,22,23,27,34].…”

Glucose administration inhibits the hepatic activation of gluconeogenesis promoted by insulin-induced hypoglycemia

“…However, the rigorous glycemic control has been related with an increased incidence of insulin induced hypoglycemia (IIH) which is the major obstacle to the implementation of the intensive treatment (Davis and Alonso, 2004). On the other hand, considering that glucagon, the most important gluconeogenic (Bracht et al, 2002) and glycogenolytic hormone (Vardanega-Peicher et al, 2003) is very expensive and has less availability, glucose is the main antidote to treat IIH (Moore and Woollard, 2005). However, previous studies (Souza et al, 2001a,b) have shown that a single intraperitoneal (ip) administration of glucose during IIH did not promote glycemia recovery.…”