GLUCOSE ENTRY INTO THE FETAL HEPATOCYTE (FH) REQUIRES NON-INSULIN DEPENDENT GLUT-1 AND GLUT-2

Abstract

Low Km glucose transporter GLUT-1 mRNA and protein is found in vivo in adult hepatocytes (AH) only with starvation and diabetes. In contrast to AH, hepatic glycogenesis during fetal life is dependent upon glucose entry into hepatocytes at low glucose concentration. We have quantitated low Km GLUT-1 mRNA as well as high Km GLUT-2 mRNA in cultured rat FH compared to male AH, as % of FH at isolation. GLUT-1 protein (immunoblot) is not present in AH at isolation, but is weakly present at 16 and 45h of culture. GLUT-1 protein is present in large amount in FH at isolation, 16 and 45h. However, 3-O-methyl glucose transport activity (1 - 30 mM) in AH and FH at 45h demonstrates the presence of two transporters (Eadie-Hofstee plot, standard enzyme kinetic assumptions). One has a Km of 23 mM, and is presumed to be GLUT-2. The second has a variable Km approximating 6-8 mM presumably related to accelerated exchange phenomena typical of GLUT-1. The Vmax at 45h culture (nM/mirvmg−1 protein) for GLUT-2 was 198 in FH and 92 in AH and for GLUT-1 was 105 in FH and 35 in AH. Therefore, activity of both GLUT-2 and GLUT-1 is greater in FH compared to AH, facilitating glucose transport at low ambient glucose levels of fetal life.