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Regulation of beta-cell glucose transporter gene expression.

Publication ,  Journal Article
Chen, L; Alam, T; Johnson, JH; Hughes, S; Newgard, CB; Unger, RH
Published in: Proc Natl Acad Sci U S A
June 1990

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 1990

Volume

87

Issue

11

Start / End Page

4088 / 4092

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • RNA, Messenger
  • Proinsulin
  • Nucleic Acid Hybridization
  • Monosaccharide Transport Proteins
  • Liver
  • Islets of Langerhans
  • Hypoglycemia
  • Hyperglycemia
 

Citation

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Chen, L., Alam, T., Johnson, J. H., Hughes, S., Newgard, C. B., & Unger, R. H. (1990). Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A, 87(11), 4088–4092. https://doi.org/10.1073/pnas.87.11.4088
Chen, L., T. Alam, J. H. Johnson, S. Hughes, C. B. Newgard, and R. H. Unger. “Regulation of beta-cell glucose transporter gene expression.Proc Natl Acad Sci U S A 87, no. 11 (June 1990): 4088–92. https://doi.org/10.1073/pnas.87.11.4088.
Chen L, Alam T, Johnson JH, Hughes S, Newgard CB, Unger RH. Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4088–92.
Chen, L., et al. “Regulation of beta-cell glucose transporter gene expression.Proc Natl Acad Sci U S A, vol. 87, no. 11, June 1990, pp. 4088–92. Pubmed, doi:10.1073/pnas.87.11.4088.
Chen L, Alam T, Johnson JH, Hughes S, Newgard CB, Unger RH. Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4088–4092.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 1990

Volume

87

Issue

11

Start / End Page

4088 / 4092

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • RNA, Messenger
  • Proinsulin
  • Nucleic Acid Hybridization
  • Monosaccharide Transport Proteins
  • Liver
  • Islets of Langerhans
  • Hypoglycemia
  • Hyperglycemia