Regulation of hepatic GLUT8 expression in normal and diabetic models.
GLUT8 is a novel glucose transporter protein that is widely distributed in tissues including liver, a central organ of regulation of glucose homeostasis. The purpose of the current study was to investigate expression and regulation of hepatic GLUT8 mRNA and protein. Therefore, Northern and immunoblot analysis, semiquantitative RT-PCR, and immunofluorescence microscopy were performed using mouse livers at different stages of embryonic and postnatal development and in type 1 (streprozotocin treated) and type 2 (GLUT4 heterozygous) diabetes. GLUT8 mRNA and protein expression in embryonic liver was differentially regulated depending on the prenatal and postnatal developmental stage of the mice. Immunofluorescence microscopy of liver from wild-type mice demonstrated the highest levels of GLUT8 protein in perivenous hepatocytes pointing to its role in regulation of glycolytic flux. In diabetic scenarios, GLUT8 mRNA levels were correlated with circulating insulin; specifically, GLUT8 mRNA decreased in a type 1 diabetes model and increased in a type 2 diabetes model, suggesting a regulatory role for insulin in GLUT8 mRNA expression. While up-regulation of GLUT8 protein occurred in both models of diabetes, only in streptozotocin diabetic livers was GLUT8 zonation altered. These data demonstrate that GLUT8 mRNA and protein are differentially regulated in liver in response to physiologic and pathologic (diabetes) milieu and suggests that GLUT8 is intimately linked to glucose homeostasis.
Gorovits
Naira
N
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cui
Lingguang
L
Busik
Julia V
JV
Ranalletta
Mollie
M
Hauguel de-Mouzon
Sylvie
S
Charron
Maureen J
MJ
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000196:embryology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000196:embryology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D017353:Gene Deletion; D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D006579:Heterozygote; D007158:Immunologic Techniques; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values
D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; C498628:Slc2a8 protein, mouse