REGULATION OF GLUT2 GLUCOSE-TRANSPORTER EXPRESSION IN LIVER BY THYROID-HORMONE - EVIDENCE FOR HORMONAL-REGULATION OF THE HEPATIC GLUCOSE-TRANSPORT SYSTEM
Sp. Weinstein et al., REGULATION OF GLUT2 GLUCOSE-TRANSPORTER EXPRESSION IN LIVER BY THYROID-HORMONE - EVIDENCE FOR HORMONAL-REGULATION OF THE HEPATIC GLUCOSE-TRANSPORT SYSTEM, Endocrinology, 135(2), 1994, pp. 649-654
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.