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.
Chen
L
L
Center for Diabetes Research, Gifford Laboratories, University of Texas Southwestern Medical Center, Dallas 75235.
Alam
T
T
Johnson
J H
JH
Hughes
S
S
Newgard
C B
CB
Unger
R H
RH
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