Co-culture of clonal beta cells with GLP-1 and glucagon-secreting cell line impacts on beta cell insulin secretion, proliferation and susceptibility to cytotoxins

Biochimie. 2016 Jun;125:119-25. doi: 10.1016/j.biochi.2016.03.007. Epub 2016 Mar 22.

Abstract

We investigated the direct effects on insulin releasing MIN6 cells of chronic exposure to GLP-1, glucagon or a combination of both peptides secreted from GLUTag L-cell and αTC1.9 alpha-cell lines in co-culture. MIN6, GLUTag and αTC1.9 cell lines exhibited high cellular hormone content and release of insulin, GLP-1 and glucagon, respectively. Co-culture of MIN6 cells with GLUTag cells significantly increased cellular insulin content, beta-cell proliferation, insulin secretory responses to a range of established secretogogues and afforded protection against exposure cytotoxic concentrations of glucose, lipid, streptozotocin or cytokines. Benefits of co-culture of MIN6 cells with αTC1.9 alphacells were limited to enhanced beta-cell proliferation with marginal positive actions on both insulin secretion and cellular protection. In contrast, co-culture of MIN6 with GLUTag cells plus αTC1.9 cells, markedly enhanced both insulin secretory responses and protection against beta-cell toxins compared with co-culture with GLUTag cells alone. These data indicate important long-term effects of conjoint GLP-1 and glucagon exposure on beta-cell function. This illustrates the possible functional significance of alpha-cell GLP-1 production as well as direct beneficial effects of dual agonism at beta-cell GLP-1 and glucagon receptors.

Keywords: GLP-1; GLUTag; Glucagon; MIN6; αTC1.9.

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects*
  • Coculture Techniques
  • Cytotoxins / pharmacology*
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Secreting Cells / metabolism*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Mice

Substances

  • Cytotoxins
  • Insulin
  • Glucagon-Like Peptide 1
  • Glucagon