The control of hepatic glucose production (HGP) and uptake (HGU) by glucose and pancreatic hormones was examined in 20 isolated livers from previable human fetuses. Livers were perfused with a synthetic recirculating medium containing either no glucose or 2.8 mM glucose. Net hepatic glucose output (NHGO) was quantified by the rise of medium glucose, HGP by dilution of [2-3H]glucose specific activity, HGU by [2-3H]glucose disappearance, and recycling of glucose carbon by the incorporation of [6-14C]glucose into [1-14C]glucose. When the perfusion medium was initially 'aglycemic', there was a transient release of glucose at a rate of 1.2 ± 0.2 μmol/min.g liver (mean ± SD); but glucose (2.8 mM) suppressed NHGO. In the absence of exogenous glucogenic substrate, HGP continued throughout the perfusion at rates exceeding 0.2 μmol/min.g, but was balanced by HGU when medium glucose was 2.8 mM. Because recycling of glucose carbon was negligible, hepatic glycogen was the predominant source of glucose and could account for all the glucose produced. Glucagon (8.7 x 10-7 M) doubled the rate of HGP and maintained a condition in which HGP slightly exceeded HGU; however, glucose 2.8 mM augmented HGU and thus attenuated NHGO after glucagon. Under the conditions of study, insulin (9.3 x 10-9 M) had no detectable effect on HGP, HGU, or NHGO. In conclusion, the predominant response of the isolated perfused human fetal liver is continuous glucose production balanced by autoregulation of hepatic glucose uptake. Acute hormonal regulation of hepatic glucose production seems to be of minor importance early in human fetal development.
|Journal||American Journal of Physiology Endocrinology Metabolism and Gastrointestinal Physiology|
|State||Published - Jan 1 1978|