REGULATION OF GLUT2 GLUCOSE-TRANSPORTER EXPRESSION IN LIVER BY THYROID-HORMONE - EVIDENCE FOR HORMONAL-REGULATION OF THE HEPATIC GLUCOSE-TRANSPORT SYSTEM

The extent to which the glucose transport system in hepatocytes is reg ulated in states of altered hepatic glucose metabolism is unclear. Bec ause thyroid hormone is known to increase hepatic glucose output, we h ypothesized that thyroid hormone might up-regulate expression of the p rincipal hepatic glucose transporter, GLUT2, facilitating increased gl ucose efflux across the hepatocyte plasma membrane. GLUT2 protein conc entration in crude liver membranes was twice as high in chronically hy perthyroid vs. hypothyroid animals, with intermediate levels in euthyr oid controls. Similar results were obtained for total GLUT2 protein, m easured in detergent extracts of liver. Northern analysis of total liv er RNA demonstrated parallel changes in GLUT2 messenger RNA (mRNA) con centration per g tissue (hypothyroid, 76 +/- 6%; euthyroid, 100 +/- 11 %; hyperthyroid, 158 +/- 12%; data expressed as percentage of mean eut hyroid values). The daily administration of a large dose of T-3 (100 m u g/100 g BW) to hypothyroid rats caused a prompt increase in hepatic GLUT2 mRNA concentration (2.5-fold at 1 day), but only a modest and gr adual change in hepatic GLUT2 protein concentration (+40% at 4 days), suggesting that the GLUT2 protein in liver may have a long half-life. We conclude that thyroid hormone regulates hepatic GLUT2 mRNA and prot ein expression. Upregulation of GLUT2 protein expression by thyroid ho rmone may serve to facilitate increased hepatic glucose output. These results suggest that the hepatic GLUT2 glucose transporter, like the e nzymes of gluconeogenesis and glycolysis, is indeed a regulatory targe t for hormones that control hepatic glucose metabolism.