Glucose intolerance is often observed after pancreatic islet
cell transplantation. The administration of
immunosuppressive agents (ISD), necessary to avoid tissue rejection, is in part responsible for
hyperglycemia. To investigate whether mouse
insulinoma (MIN6) cells transfected with the
glucagon like peptide-1 (GLP-1) fragment of the
proglucagon gene (RIP/
GLP-1 MIN6 cells) are resistant to the toxicity derived from the administration of ISD. RIP/
GLP-1 MIN6 cells, as well as parental MIN6 cells, were exposed to a cocktail of ISD. The secretion of
insulin and the expression of apoptosis-related
proteins were investigated by RIA and western blot analysis. Cell apoptosis was quantified by FACS analysis. Finally, to study whether the antiapoptotic action of
GLP-1 was a function of its effect on insulin secretion, or rather it was a direct effect of
GLP-1, cells were cultured with or without
diazoxide or exendin-9.
GLP-1 improved the functional activity and the viability of cells exposed to ISD. The insulin secretion of RIP/
GLP-1 MIN6 cells after exposure to ISD was preserved. The expression of
GLP-1 by beta-cells reduced the number of apoptotic cells and increased the expression of the antiapoptotic
protein Bcl-2.
GLP-1 also decreased the abundance of the proapoptotic markers PARP-p85 and Smac/Diablo. Treatment of cells with the
diazoxide did not abolish the protective advantage that cells transfected with
GLP-1 had; conversely the exposure of cells to exendin-9 was associated with a restored susceptibility to apoptosis. This report demonstrates that
GLP-1 is capable of preserving beta-cell function and protecting cells from apoptotic cell death.