Adrenalectomy (adx) induces hypoglycemia by decreasing hepatic gluconeogenesis and glycogenolysis by lowering the response to glycogenolytic and gluconeogenic stimuli Adx also produces large changes in liver cell Ca metabolism. Our plan is to assess the contribution of these changes in cell Ca and of the Ca-dependent Alpha-adrenergic pathway to the effects of adrenalectomy on hepatic glycogenolysis. We will investigate the effects of adx and of glucocorticoids on the various steps involved in the Ca-dependent pathway of phosphorylase activation: Alpha-receptor density, phosphatidyl inositol and myo-inositol 1,4,5-triphosphate, cytosolic free calcium, sequestration and mobilization of Ca in and out of mitochondria and of endoplasmic reticulum, Ca-dependent regulatory proteins or calmodulin and the contribution of other factors such as a low total phosphorylase. We will determine the time course of the appearance of the disturbance in hepatocyte Ca metabolism and how rapidly the changes can be corrected by the administration of glucocorticoids. We will also study whether hyperadrenocorticism induced by the administration of high concentrations of glucocorticoids produces changes in hepatocyte Ca metabolism opposite to those observed in adx.
