Regulation of gluconeogenesis by norepinephrine, vasopressin, and angiotensin II: a comparative study in the absence and presence of extracellular Ca2+1

In hepatocytes isolated from fasted rats, vasopressin and angiotensin II stimulate the rate of gluconeogenesis from lactate or pyruvate in a Ca2+-dependent manner similar to that previously reported for norepinephrine. Actions of the peptide hormones on gluconeogenesis from glycerol or sorbitol, reduced substrates that require oxidation before they enter the gluconeogenic pathway at triosephosphate, also resemble those of norepinephrine. Stimulation of glucose production from these substrates is observed only in the presence of extracellular Ca2+. Actions of the peptide hormones on gluconeogenesis from dihydroxyacetone or fructose, the oxidized counterparts of glycerol and sorbitol, respectively, do not resemble those of norepinephrine. While norepinephrine enhances rates of glucose production from dihydroxyacetone or fructose in the absence of extracellular Ca2+, vasopressin and angiotensin II are ineffective either in the absence or presence of extracellular Ca2+. When the oxidation-reduction state in hepatocytes metabolizing dihydroxyacetone is altered by adding an equimolar concentration of ethanol (to provide cytosolic reducing equivalents), the results are similar to those obtained when cells are incubated with the reduced counterpart of dihydroxyacetone, glycerol, i.e., the peptide hormones cause an apparent increase in the rate of glucose production in a Ca2+-dependent manner. If, on the other hand, hepatocytes are incubated with glycerol or sorbitol and an equimolar concentration of pyruvate (to provide a cytosolic hydrogen acceptor), the peptide hormones, unlike norepinephrine, are ineffective in stimulating gluconeogenesis in the absence of extracellular Ca2+. These results indicate that whereas many of the actions of vasopressin and angiotensin II are similar to those of alpha 1-adrenergic agents, there are major differences in the manner in which the hormones act at various sites to regulate gluconeogenesis.