Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

Abstract

The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a threeto fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepatic venules. Starvation-dependent expression of the erythroid/ brain GT on the plasma membrane of these additional hepatocytes is lost within 3 h of glucose refeeding; however, by immunoblotting we show that the protein is still present. Its loss from the surface is possibly explained by internalization. (J.Clin. Invest. 1990. 86:986-992.) Key words: starvation * liver glucose transporter * glucose refeeding * regulation and internalization Introduction The liver plays a key role in glucose homeostasis. Of the blood entering the liver, 75% comes from the digestive system via the portal vein and 25% from the hepatic artery. During passage of blood through the liver, glucose in excess of 5 mM (after a meal) is removed; it is either stored as glycogen or catabolized by glycolysis. Between meals and during starvation, when blood glucose is lower then 5 mM, hepatic glycogen degradation and gluconeogenesis result in release of glucose into the blood. Thus, constant blood glucose concentration is maintained by the parenchymal cells (hepatocytes).

Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells.

“…2B) and was not seen in untransfected cells or in cells transfected with the vector lacking the GLUT-2 insert (data not shown). Thus, AtT-20ins cells not only have the capacity to produce GLUT-2 mRNA and protein but also sort the protein to the cell membrane, as occurs in islets and liver (18,(28)(29)(30).…”

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

“…Another possibility is that in both control and MLP livers, glucose uptake was limited by some other step, such as glucose transport into the hepatocyte, which might have differed in its activity in the two groups. The facilitative glucose transporter GLUT2 is expressed in the plasma membranes of hepatocytes in all zones of the lobule, and has a high K m for glucose (10-15 mM); the GLUT1 transporter (K m for glucose 1-2 mM) is expressed in the plasma membrane only in the most perivenous cells, though the anatomical extent of its expression is somewhat increased by starvation (24). An argument against either transporter being rate-limiting in control livers is the observation that transfection of rat hepatoma cells in primary culture with an adenovirus containing the glucokinase gene resulted in a striking increase in glucose uptake (25); furthermore, it has been shown (26) that disruption of the glucokinase gene in mice, resulting in ϩ/Ϫ heterozygotes, causes a lower liver GK activity (by 37%), and significantly reduced liver glucose phosphorylation flux.…”

Position-specific Gene Expression in the Liver Lobule Is Directed by the Microenvironment and Not by the Previous Cell Differentiation State

“…Some genes are expressed throughout the liver lobule, whereas others exhibit gradients between portal and perivenous areas (1)(2)(3)(4)(5)(6)(7)(8)(9). Associations between transcriptional gene switching, such as albumin and ␣-fetoprotein genes, and selective gene expression during development, as seen for cytochrome P450 genes have been interpreted in the context of cell differentiation mechanisms (10 -12).…”