Differential Regulation of Two Glucose Transporters in Rat Liver by Fasting and Refeeding and by Diabetes and Insulin Treatment

Two species of glucose transporter (GT) are present in the liver: the erythroid/brain GT and the newly characterized liver GT. No information is available regarding the functional role of these two species or whether their expression is regulated concordantly in states in which hepatic glucose uptake or output are markedly altered. In this study, we analyzed the effect of fasting and refeeding and streptozocin-induced diabetes and subsequent insulin treatment on the expression of the erythroid/brain and liver GT polypeptides and their mRNAs in rat liver. The erythroid/brain GT mRNA in livers of control rats corresponded to 1–3% of the amount of liver GT mRNA. After a 4-day fast, its level increased ∼3-fold and represented 8–10% of the liver GT mRNA, whereas the corresponding protein increased 4-fold. In livers from diabetic rats, levels of the erythroid/brain GT mRNA increased up to 2.4-fold and gradually returned to normal with chronic insulin treatment. Levels of the corresponding protein were minimally altered. Levels of immunoreactive liver GTs were not significantly changed by 2 days of fasting, 7 or 14 days of diabetes, or subsequent insulin treatment for 3, 5, or 7 days but increased up to 75% with refeeding for 3–48 h. Liver GT mRNA levels minimally decreased in diabetic or insulin-treated rats, decreased 45% after a 2-day fast, and increased up to 5-fold on refeeding for 24 h. These results indicate that 1) the liver GT is the main transporter species in the liver, 2) its expression is not affected by the altered metabolic states studied, with the exception of a slight elevation with refeeding, and 3) erythroid/brain GT expression in liver is increased by fasting. Because regulation of the erythroid/brain GT in liver is unlike its regulation in adipocytes under the same metabolic conditions, this indicates that the control of its expression is tissue specific. Furthermore, the two species of GTs in the liver are differentially regulated, and posttranscriptional events play a major role in determining their level of expression.