Modulation by sodium butyrate of the differentiated status of a clonal pancreatic B-cell line (RIN)

Diabetes Res. 1989 Oct;12(2):93-9.

Abstract

RINmRH cells are a cloned cell line derived from a transplantable rat insulinoma. These cells display only some of the differentiated structure/function features of native pancreatic B-cells. In particular, they do not efficiently or reproducibly express islet B-cell surface antigens, which would otherwise render them useful for screening for the presence of anti-islet cell surface antibodies in the serum of suspected diabetic patients or their relatives. This study examines whether sodium butyrate can enhance expression of B-cell differentiation antigens on RIN cells. RIN cells were exposed to 1,2 or 4 mM butyrate for nine days, and cell growth followed. At 1 mM, butyrate inhibited cell growth by 90%. At the higher concentrations, there was a net loss in the number of cells per culture dish. Exposing the cells to 1 mM or 2 mM butyrate for two days, resulted in a 50% increase in cellular insulin content at the expense of a partial (1 mM) or complete (2 mM) loss of stimulated insulin release in response to glyceraldehyde or serine. A concentration of 1 mM butyrate was therefore used for subsequent studies. The binding to RIN cells of a panel of monoclonal antibodies (mAb's) known to bind native islet cells (R2D6, A2B5, A1D2, 3G5) as well as of serum from a diabetic patient known to carry anti-islet cell antibodies, was screened by cytofluorography or by a radio-binding assay. The relative binding affinity of the mAb's was 3G5 greater than A1D2 greater than A2B5 greater than R2D6. Only 2-3% of the cells were bound by the diabetic patient serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Autoantibodies / analysis
  • Butyrates / pharmacology*
  • Butyric Acid
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Culture Techniques / methods
  • DNA, Neoplasm / analysis
  • Diabetes Mellitus / blood
  • Flow Cytometry / methods
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulinoma
  • Pancreatic Neoplasms
  • Tumor Cells, Cultured / cytology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / immunology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Butyrates
  • DNA, Neoplasm
  • Insulin
  • islet cell antibody
  • Butyric Acid