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PMID: 7593639 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.

The Journal of clinical investigation ·Vol. 96 ·No. 5 ·1995-11-00 ·Pages 2489-95

De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F

Abstract

Glucose homeostasis is controlled by a glucose sensor in pancreatic beta-cells. Studies on rodent beta-cells have suggested a role for GLUT2 and glucokinase in this control function and in mechanisms leading to diabetes. Little direct evidence exists so far to implicate these two proteins in glucose recognition by human beta-cells. The present in vitro study investigates the role of glucose transport and phosphorylation in beta-cell preparations from nondiabetic human pancreata. Human beta-cells differ from rodent beta-cells in glucose transporter gene expression (predominantly GLUT1 instead of GLUT2), explaining their low Km (3 mmol/liter) and low VMAX (3 mmol/min per liter) for 3-O-methyl glucose transport. The 100-fold lower GLUT2 abundance in human versus rat beta-cells is associated with a 10-fold slower uptake of alloxan, explaining their resistance to this rodent diabetogenic agent. Human and rat beta-cells exhibit comparable glucokinase expression with similar flux-generating influence on total glucose utilization. These data underline the importance of glucokinase but not of GLUT2 in the glucose sensor of human beta-cells.

MeSH Terms
Animals Cells, Cultured Gene Expression Glucokinase/biosynthesis,genetics Glucose/metabolism Glucose Transporter Type 1 Glucose Transporter Type 2 Humans Islets of Langerhans/metabolism Monosaccharide Transport Proteins/biosynthesis,genetics Phosphorylation Rats
Chemicals
Glucose Transporter Type 1 Glucose Transporter Type 2 Monosaccharide Transport Proteins SLC2A1 protein, human Slc2a1 protein, rat Glucokinase Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
De Vos A
Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Heimberg H
Quartier E
Huypens P
Bouwens L
Pipeleers D
Schuit F
References (39)
39 references, click to expand
  1. Mechanisms of glucose stimulated insulin secretion in health and in diabetes: some re-evaluations and proposals.
    Diabetologia. 1975 Feb;11(1):1-13 PMID: 166897
  2. Differences in glucose transporter gene expression between rat pancreatic alpha- and beta-cells are correlated to differences in glucose transport but not in glucose utilization.
    J Biol Chem. 1995 Apr 14;270(15):8971-5 PMID: 7721807
  3. Kinetic properties of the reconstituted glucose transporter from human erythrocytes.
    J Biol Chem. 1981 Sep 10;256(17):8907-14 PMID: 6455434
  4. Regulation of glucose metabolism in pancreatic islets.
    Diabetes. 1981 Nov;30(11):911-22 PMID: 6271617
  5. Differences in glucose handling by pancreatic A- and B-cells.
    J Biol Chem. 1984 Jan 25;259(2):1196-200 PMID: 6141162
  6. The glucokinase glucose sensor in human pancreatic islet tissue.
    Diabetes. 1986 Jan;35(1):61-7 PMID: 3510141
  7. Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.
    Proc Natl Acad Sci U S A. 1986 Apr;83(7):1998-2001 PMID: 3515342
  8. Functional specialization of different hepatocyte populations.
    Physiol Rev. 1989 Jul;69(3):708-64 PMID: 2664826
  9. Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8688-92 PMID: 2479026
  10. The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence.
    J Biol Chem. 1990 Apr 25;265(12):6548-51 PMID: 2182619
  11. Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes.
    Diabetes. 1990 Jun;39(6):647-52 PMID: 2189759
  12. Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes.
    Science. 1990 Oct 26;250(4980):546-9 PMID: 2237405
  13. Reduced beta-cell glucose transporter in new onset diabetic BB rats.
    J Clin Invest. 1990 Nov;86(5):1615-22 PMID: 2243134
  14. Elusive proximal signals of beta-cells for insulin secretion.
    Diabetes. 1990 Dec;39(12):1461-6 PMID: 2245873
  15. Differential localization of two glucose transporter isoforms in rat kidney.
    Am J Physiol. 1990 Dec;259(6 Pt 1):C286-94 PMID: 2260638
  16. Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells.
    Science. 1991 Mar 8;251(4998):1200-5 PMID: 2006409
  17. Expression of human glucose transporters in Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte, liver, and brain isoforms.
    Biochemistry. 1991 May 28;30(21):5139-45 PMID: 2036379
  18. Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):688-92 PMID: 1309953
  19. Glucose transporter levels in tissues of spontaneously diabetic Zucker fa/fa rat (ZDF/drt) and viable yellow mouse (Avy/a).
    Diabetes. 1992 Feb;41(2):187-93 PMID: 1733808
  20. Glucokinase gene is genetic marker for NIDDM in American blacks.
    Diabetes. 1992 Jul;41(7):843-9 PMID: 1612198
  21. The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment.
    J Clin Invest. 1992 Jul;90(1):77-85 PMID: 1634622
  22. Roles of insulin resistance and beta-cell dysfunction in dexamethasone-induced diabetes.
    J Clin Invest. 1992 Aug;90(2):497-504 PMID: 1644920
  23. Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young.
    Lancet. 1992 Aug 22;340(8817):444-8 PMID: 1354782
  24. Expression and function of GLUT-1 and GLUT-2 glucose transporter isoforms in cells of cultured rat pancreatic islets.
    J Biol Chem. 1992 Aug 25;267(24):17241-7 PMID: 1512261
  25. Expression of the brain-type glucose transporter is restricted to brain and neuronal cells in mice.
    Diabetologia. 1992 Apr;35(4):304-9 PMID: 1516757
  26. Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function.
    J Clin Invest. 1992 Oct;90(4):1263-8 PMID: 1401063
  27. Linkage analysis of GLUT1 (HepG2) and GLUT2 (liver/islet) genes in familial NIDDM.
    Diabetes. 1992 Dec;41(12):1660-7 PMID: 1359987
  28. Abnormal facilitative glucose transporter gene expression in human islet cell tumors.
    J Clin Endocrinol Metab. 1993 Jan;76(1):75-8 PMID: 8421107
  29. Transfection of AtT-20ins cells with GLUT-2 but not GLUT-1 confers glucose-stimulated insulin secretion. Relationship to glucose metabolism.
    J Biol Chem. 1993 Jul 15;268(20):15205-12 PMID: 8325893
  30. Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport.
    EMBO J. 1993 Jul;12(7):2873-9 PMID: 8335003
  31. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene.
    J Clin Invest. 1993 Nov;92(5):2092-8 PMID: 8227324
  32. Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion.
    Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2051-5 PMID: 7510884
  33. GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release. Relationship to glucokinase activity.
    J Biol Chem. 1994 Apr 15;269(15):11523-9 PMID: 8157682
  34. A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity.
    J Biol Chem. 1994 Jul 8;269(27):17765-7 PMID: 8027028
  35. STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells.
    Diabetes. 1994 Nov;43(11):1326-33 PMID: 7926307
  36. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9253-6 PMID: 7937750
  37. Expression of GLUT-2 antisense RNA in beta cells of transgenic mice leads to diabetes.
    J Biol Chem. 1994 Nov 18;269(46):28543-6 PMID: 7961797
  38. Loss of glucose-induced insulin secretion and GLUT2 expression in transplanted beta-cells.
    Diabetes. 1995 Jan;44(1):75-9 PMID: 7813817
  39. Alloxan uptake by isolated rat islets of Langerhans.
    Endocrinology. 1978 Jun;102(6):1847-55 PMID: 369835
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1995-11-00
Pages
2489-95
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC185903
Subset
IM
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