Comparative studies on the influence of hormones on metabolite compartmentation in isolated liver cells during gluconeogenesis from lactate.

Gluconeogenesis from lactate in isolated hepatocytes is activated by a variety of hormonal stimuli. As to the mechanism(s) of action, it is widely accepted that the effect of glucagon is mediated by cyclic AMP (Exton et al., 1970, 1971), and adrenaline and phenylephrine have been shown to activate gluconeogenesis without involvement of cyclic AMP (Tolbert et al., 1973; Tolbert & Fain, 1974; Kneer et al., 1974; Exton & Harper, 1975; Hutson et al., 1976; Cherrington et al., 1976). Moreover, vasopressin has been demonstrated to increase glucose production in the perfused liver (Hems & Whitton, 1973) independently of changes in the hepatic cyclic AMP content (Kirk & Hems, 1974). Recently we have reported on the subcellular distridtion of metabolites in isolated hepatocytes after incubation with glucagon, which is known to cause a large increase in cyclic AMP (Johnson et al., 1972; Ingebretsen et al., 1972; Kirk & Hems, 1974;Christoffersen &Berg, 1974; Exton &Harper, 1975; Hutsonet al., 1976; Cherrington et al., 1976; Hems et al., 1978). The present study is concerned with the question of what changes in metabolite compartmentation might occur when liver cells are incubated with dibutyryl cyclic AMP or with glucogenic agents that cause either a relatively small increase or no change in cellular cyclic AMP, such as adrenaline and isoproterenol (Tolbert et al., 1973; Exton & Harper, 1975; Hutson et al., 1976; Chan & Exton, 1977) or phenylephrine (Exton & Harper, 1975; Hutson et al., 1976; Cherrington et al., 1976; Chan & Exton, 1977) and vasopressin (Kirk & Hems, 1974; Hems et al., 1978) respectively. Surprisingly, the effects of dibutyryl cyclic AMP on metabolite distribution proved to be different from those produced by glucagon.