Effect of Feeding and Fasting on the Early Steps of Glucagon Action in Isolated Rat Liver Cells

Abstract

The effect of the nutritional state (fasted or fed) on the binding of glucagon and on the glucagon-stimulated cyclic AMP accumulation in the presence of theophylline was studied in isolated rat liver cells. The binding of glucagon was higher in cells from fed than in those from fasted rats at each concentration of glucagon tested between 0.1 and 36 nM. The specific binding of the hormone was about 2-fold higher in cells from fed than from fasted rats. At concentrations of glucagon between 0.1 and 2.2 nM, the accumulation of cyclic AMP in the presence of 1 mM theophylline was higher in the cells from fed rats. Furthermore, 4 times as much glucagon was required to elicit half-maximal cyclic AMP accumulation in the cells of fasted (1.47 nM) than in the cells of fed (0.35 nM) rats. These data suggest that, in isolated rat liver cells, both glucagon binding to receptor sites and glucagon-stimulated cyclic AMP levels in the presence of theophylline can be affected by the nutritional status of the animal.

Glucagon Binding and Adenylate Cyclase Activity in Liver Membranes from Untreated and Insulin-Treated Diabetic Rats

“…Both decreased and increased binding of glucagon have been reported in association with hyperglucagonemia. Thus, in starvation (34) and in association with continuous administration of exogenous glucagon,1 a decrease in glucagon 1 Soman, V., and P. Felig. Unpublished observations.…”

Reduced sensitivity of the hepatic adenylate cyclase-cyclic AMP system to glucagon during sustained hormonal stimulation.

“…A reduction in hormone binding induced by prior exposure of cells to hormone has been previously reported (39,40), but the role of altered glucagon binding in the decline in hormonal responsiveness observed in the present study remains to be determined. In this regard, it is of interest that Fouchereau and co-workers have recently reported that hepatic binding of glucagon is diminished in rats after a 48-h fast, when endogenous glucagon levels are increased (41).…”

“…Such "desensitization" of hormone-responsive AC by prior exposure of tissue to the hormone might serve to limit energetically wasteful cAMP generation during periods of prolonged stimulation. Whether such changes have physiologic significance is at present conjectural, but as noted above, reductions in both hepatic binding (41) and in hepatic cAMP responsiveness to glucagon (5) may occur during periods of sustained endogenous hyperglucagonemia.…”

Glucagon binding to purified liver plasma membranes from growing rats undergoing energy restriction

“…Therefore, the drop in apparent specific !z51_glucagon binding per mg of purified liver plasma membranes could be explained by a drop in membrane purity. Alternatively, 5'-nucleotidase activity could have decreased as a result of energy restriction (Grizard, Arnal and Pion, 1980 The decrease in glucagon binding to its receptors after feeding the experimental diet correlates with the decrease in glucagon binding found in fasted rats (Fouchereau-Peron et al, 1976 ;Broer et al, 1977 ;Caro and Amatruda, 1980 ;Srikant et al, 1977 ;Freeman et al, 1977). It contrasts with the constant, glucagon binding to isolated hepatocytes found in restricted goats (Gill and Hart, 1979 ;Gill and Hart, 19811.…”

“…Glucagon binding to cell surface receptors is generally believed to be the initial step in glucagon action, controlling the latter in vitro. A decrease in glucagon binding to its liver receptors accompanies a decrease in glucagon action in fasted rats (Fouchereau-Peron et al, 1976 ;Broer et al, 1977). However, glucagon binding does not always correlate with glucagon sensitivity status in hyperglucagonemic and fasted rodents Caro and Amatruda, 1980 (Rérat and Desmoulin, 1970).…”