Endocrinology and Metabolism

Determinants of glucose toxicity and its reversibility in the pancreatic islet β-cell line, HIT-T15

Catherine E. Gleason, Michael Gonzalez, Jamie S. Harmon, R. Paul Robertson


HIT-T15 cells, a clonal β-cell line, were cultured and passaged weekly for 6 mo in RPMI 1640 media containing various concentrations of glucose. Insulin content decreased in the intermediate- and late-passage cells as a continuous rather than a threshold glucose concentration effect. In a second series of experiments, cells were grown in media containing either 0.8 or 16.0 mM glucose from passages 76 through105. Subcultures of passages 86, 92,and 99 that had been grown in media containing 16.0 mM glucose were switched to media containing 0.8 mM glucose and also carried forward to passage 105. Dramatic increases in insulin content and secretion and insulin gene expression were observed when the switches were made at passages 86 and 92but not when the switch was made at passage 99. These findings suggest that glucose toxicity of insulin-secreting cells is a continuous rather than a threshold function of glucose concentration and that the shorter the period of antecedent glucose toxicity, the more likely that full recovery of cell function will occur.

  • insulin gene expression
  • PDX-1 binding


  • Address for reprints and other correspondence: R. Paul Robertson, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122 (E-mail: rpr{at}u.washington.edu).

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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