Regulation of beta-cell glucose transporter gene expression.
It has been postulated that a glucose transporter of beta cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, we subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated beta-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia (glucose at 29 +/- 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days (blood glucose at 57 +/- 7 mg/dl vs. 120 +/- 10 mg/dl in saline-infused control rats), GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively (P = 0.001). After 12 days (glucose at 54 +/- 8 mg/dl), GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%. After 12 days of hypoglycemia, the Km for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high Km glucose transporter in beta cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, we also infused animals with 50% (wt/vol) glucose for 5 days (glucose at 200 +/- 50 mg/dl). Hyperglycemic clamping increased GLUT-2 mRNA by 46% (P = 0.001) whereas proinsulin mRNA doubled (P = 0.001). We conclude that GLUT-2 expression in beta cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.
Center for Diabetes Research, Gifford Laboratories, University of Texas Southwestern Medical Center, Dallas 75235.
L
L
Chen
T
T
Alam
J H
JH
Johnson
S
S
Hughes
C B
CB
Newgard
R H
RH
Unger
D000818:Animals; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000235:genetics*; D007003:Hypoglycemia / Q000235:genetics*; D007515:Islets of Langerhans / Q000502:physiology*; D008099:Liver / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011384:Proinsulin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011384:Proinsulin