Functional analysis of a conditionally transformed pancreatic β-cell line

Norman Fleischer, Chuan Chen, Manju Surana, Margarita Leiser, Luciano Rossetti, William Pralong, Shimon Efrat

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Development of β-cell lines for cell therapy of diabetes is hindered by functional deviations of the replicating cells from the normal β-cell phenotype. In a recently developed cell line, denoted βTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) gene regulatory system, growth arrest can be induced by shutting off Tag expression in the presence of Tc. Here, we compared differentiated cell functions in dividing and growth-arrested βTC-tet cells, both in culture and in vivo. Proliferating cells stably maintained normal glucose responsiveness for >60 passages in culture. Growth-arrested cells survived for months in culture and in vivo and maintained normal insulin production and secretion. After growth arrest, the cells gradually increased their insulin content three- to fourfold. This occurred without significant changes in insulin biosynthetic rates. At high passage numbers, proliferating βTC-tet cells exhibited an abnormal increase in hexokinase expression. However, the upregulation of hexokinase was reversible upon growth arrest. Growth-arrested cells transplanted intraperitoneally into syngeneic recipients responded to hyperglycemia by a significant increase in insulin secretion. These findings demonstrate that transformed β-cells maintain function during long periods of growth arrest, suggesting that conditional transformation of β-cells may be a useful approach for developing cell therapy for diabetes.

Original languageEnglish (US)
Pages (from-to)1419-1425
Number of pages7
JournalDiabetes
Volume47
Issue number9
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Fleischer, N., Chen, C., Surana, M., Leiser, M., Rossetti, L., Pralong, W., & Efrat, S. (1998). Functional analysis of a conditionally transformed pancreatic β-cell line. Diabetes, 47(9), 1419-1425. https://doi.org/10.2337/diabetes.47.9.1419