Glucose transporter isotypes switch in T-antigen-transformed pancreatic β cells growing in culture and in mice

M. Tal, B. Thorens, M. Surana, N. Fleischer, H. F. Lodish, D. Hanahan, S. Efrat

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Abstract

High-level expression of the low-K(m) glucose transporter isoform GLUT-1 is characteristic of many cultured tumor and oncogene-transformed cells. In this study, we tested whether induction of GLUT-1 occurs in tumors in vivo. Normal mouse β islet cells express the high-K(m) (~20 mM) glucose transporter isoform GLUT-2 but not the low-K(m) (1 to 3 mM) GLUT-1. In contrast, a β cell line derived from an insulinoma arising in a transgenic mouse harboring an insulin-promoted simian virus 40 T-antigen oncogene (βTC3) expressed very low levels of GLUT-2 but high levels of GLUT-1. GLUT-1 protein was not detectable on the plasma membrane of islets or tumors of the transgenic mice but was induced in high amounts when the tumor-derived βTC3 cells were grown in tissue culture. GLUT-1 expression in secondary tumors formed after injection of βTC3 cells into mice was reduced. Thus, high-level expression of GLUT-1 in these tumor cells is characteristic of culture conditions and is not induced by the oncogenic transformation; indeed, overnight culture of normal pancreatic islets causes induction of GLUT-1. We also investigated the relationship between expression of the different glucose transporter isoforms by islet and tumor cells and induction of insulin secretion by glucose. Prehyperplastic transgenic islet cells that expressed normal levels of GLUT-2 and no detectable GLUT-1 exhibited an increased sensitivity to glucose, as evidenced by maximal insulin secretion at lower glucose concentrations, compared with that exhibited by normal islets. Further, hyperplastic islets and primary and secondary tumors expressed low levels of GLUT-2 and no detectable GLUT-1 on the plasma membrane; these cells exhibited high basal insulin secretion and responded poorly to an increase in extracellular glucose. Thus, abnormal glucose- induced secretion of insulin in prehyperplastic islets in mice was independent of changes in GLUT-2 expression and did not require induction of GLUT-1 expression.

Original languageEnglish (US)
Pages (from-to)422-432
Number of pages11
JournalMolecular and cellular biology
Volume12
Issue number1
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tal, M., Thorens, B., Surana, M., Fleischer, N., Lodish, H. F., Hanahan, D., & Efrat, S. (1992). Glucose transporter isotypes switch in T-antigen-transformed pancreatic β cells growing in culture and in mice. Molecular and cellular biology, 12(1), 422-432.