GLUCOSE REGULATION OF GLUCOSE TRANSPORTERS IN CULTURED ADULT AND FETAL HEPATOCYTES

GLUT2 is the major glucose transporter of adult hepatocytes. In vivo, membrane GLUT1 is localized to a ring of perivenous cells and increase s slightly after fasting or insulin deprivation. GLUT1 also increases in vitro after prolonged culture of isolated adult hepatocytes. We hav e previously shown that GLUT1 mRNA, protein, and activity are present in the rat fetal hepatocyte, and that both GLUT1 and GLUT2 are importa nt for the pattern of glucose transport in the fetal hepatocyte, We te sted the hypothesis that the postnatal increase in circulating glucose is one of the regulators of the changed pattern of GLUT1 and GLUT2 in the hepatocyte after the fetal to neonatal transition. Fetal and adul t rat hepatocytes were cultured for 45 hours in supplemented Dulbecco' s modified Eagle's medium at glucose concentrations of 1, 8.3, or 30 m mol/L. Culture at 8.3 and 30 mmol/L glucose diminished GLUT1 mRNA as c ompared with culture in 1 mmol/L glucose in both fetal and adult hepat ocytes (P <.05), but GLUT1 mRNA levels were lower in adult versus feta l hepatocyte cultures at 8.3 and 30 mmol/L (P <.05). Similarly, GLUT1 protein levels were significantly diminished in hepatocytes cultured a t higher medium glucose (P <.05 for fetal cells at 30 v 1 mmol/L; P <. 05 for adult cells at 8.3 and 30 v 1 mmol/L). GLUT2 mRNA abundance was enhanced by medium glucose in adult hepatocytes (P <.05 at 8.3 and 30 v 1 mmol/L) and was unchanged by medium glucose in fetal hepatocytes. In contrast, GLUT2 protein level was unchanged by medium glucose in a dult hepatocytes, and was diminished at 30 mmol/L as compared with 1 m mol/L glucose in fetal hepatocytes (P < .05). In confirmation of these findings, uptake of a-deoxyglucose (2-DOG) by fetal hepatocytes was s ignificantly diminished after culture in 8.3 or 30 mmol/L glucose vers us 1 mmol/L glucose (P <.05 and <.01, respectively). These studies con firm that the fetal hepatocyte glucose transporter pattern could be ma intained in part by low fetal portal glucose levels. However, the resi stance of the fetal hepatocyte glucose transporter pattern as compared with that of the adult hepatocyte to the effects of hyperglycemia sug gests additional undefined control mechanisms. Copyright (C) 1995 by W .B. Saunders Company