Glucose production in the newborn dog. II. Evaluation of autonomic and enzymatic control in the isolated perfused canine liver.

The effects of birth and morepinephrine on hepatic glucose production, glycogenolysis, and gluconeogenesis were examined in livers isolated from fetal dogs at term, littermates 3 hr after delivery, and newborn dogs 1-5 days old. Livers were perfused in pairs with medium containing (6-3H)glucose (6 mM) and (3-14C)lactate (10 mM +/- a pharmacologic amount of norepinephrine (10(-6)M). Changes in glucose production rates were correlated with changes in the enzymatic activities controlling gluconeogenesis. Net glucose production was less than 0.48 mumol/min-g liver both fetal and 3 hr liver but stablized above 1 mumol/min-g later during the first day. Initially, mobilization of the fetal hepatic glycogen accounted for glucose output. Subsequently, incorporation of lactate into glucose rose from negligible fetal rates to 0.19 mumol/min-g and accounted for 21% of net glucose production on day 3. Mazimal pyruvate carboxylase activity and mitochondrial CO2 fixation increased postnatally and correlated directly with net glucose production, glucose production from glycogen, and glucose production from lactate. Fetal liver did not respond to norepinephrine. Thereafter, norepinephrine increase hepatic glucose production by stimulating glycogen breakdown. Postnatal acceleration of glucose production and the response to norepinephrine occurred only after indiction of mitochondrial CO3 fixation. During day 1 the decline of hepatic glycogen in response to norepinephrine correlated with both CO2 fixation and lactate incorporation into glucose. Thus, initiation of gluconegenesis after birth may have been required for the postnatal acceration of hepatic glucose production and for the regulation of glycogenolysis by norpinephrine.