EFFECTS OF LACTATE INFUSION ON HEPATIC GLUCONEOGENESIS AND GLYCOGENOLYSIS

Endogenous glucose production rate (EGPR) remains constant when lactat e is infused in healthy humans. A decrease of glycogenolysis or of glu coneogenesis from endogenous precursors or a stimulation of glycogen s ynthesis, may all be involved; This autoregulation does not depend on changes in glucoregulatory hormones. It may be speculated that alterat ions in basal sympathetic tone may be involved. To gain insights into the mechanisms responsible for autoregulation of EGPR, glycogenolysis and gluconeogenesis were measured, with a novel method (based on the p relabelling of endogenous glycogen with C-13 glucose, and determinatio n of hepatic C-13 glycogen enrichment from breath (CO2)-C-13 and respi ratory gas exchanges) in healthy humans infused with lactate or saline . These measurements were performed with or without beta-adrenergic re ceptor blockade (propranolol). Infusion of lactate increased energy ex penditure, but did not increase EGPR; the relative contributions of gl uconeogenesis and glycogenolysis to EGPR were also unaltered. This ind icates that autoregulation is attained, at least in part, by inhibitio n of gluconeogenesis from endogenous precursors. beta-adrenergic recep tor blockade alone (with propranolol) did not alter EGPR, glycogenolys is or gluconeogenesis. During infusion of lactate, propranolol decreas ed the thermic effect of lactate but EGPR remained constant. This indi cates that alterations of beta-adrenergic activity is not required for autoregulation of EGPR.