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 increases slightly after fasting or insulin deprivation. GLUT1 also increases in vitro after prolonged culture of isolated adult hepatocytes. We have previously shown that GLUT1 mRNA, protein, and activity are present in the rat fetal hepatocyte, and that both GLUT1 and GLUT2 are important for the pattern of glucose transport in the fetal hepatocyte. We tested the hypothesis that 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 adult rat hepatocytes were cultured for 45 hours in supplemented Dulbecco's modified Eagle's medium at glucose concentrations of 1, 8.3, or 30 mmol/L. Culture at 8.3 and 30 mmol/L glucose diminished GLUT1 mRNA levels were lower in adult versus fetal hepatocyte cultures at 8.3 and 30 mmol/L (P < .05). Similarly, GLUT1 protein levels were significantly diminished in hepatocytes cultured at 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 adult hepatocytes, and was diminished at 30 mmol/L as compared with mmol/L glucose in fetal hepatocytes (P < .05). In confirmation of these findings, uptake of 2-deoxyglucose (2-DOG) by fetal hepatocytes was significantly diminished after culture in 8.3 or 30 mmol/L glucose versus 1 mmol/L glucose (P < .05 and < .01, respectively). These studies confirm that the fetal hepatocyte glucose transporter pattern could be maintained in part by low fetal portal glucose levels. However, the resistance of the fetal hepatocyte glucose transporter pattern as compared with that of the adult hepatocyte to the effects of hyperglycemia suggests additional undefined control mechanisms.
Zheng
Q
Q
Pediatric Endocrine Unit, Massachusetts General Hospital.
Levitsky
L L
LL
Mink
K
K
Rhoads
D B
DB
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000502:physiology*; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D005947:Glucose