Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Aim An adequate beta cell number is important to prevent the onset and development of type 2 diabetes. The aim of this study was to determine if phytoestrogen gesintein has protective effects against high glucose-induced cell apoptosis in human pancreas cells, and to try to determine the possible mechanism for this protection. Methods Human pancreatic beta cells were subjected to normal (5 mM) or high glucose (25 mM) with and without the presence of 100nM genistein, and also in the presence and absence of the pure anti-estrogen ICI-182780 (100 nM). Bcl-2 siRNA transfection was performed to investigate if the effect of genistein was also Bcl-2 dependent. Cell proliferation and apoptosis were determined by Tritiated Thymidine Incorporation Assay and Cell Apoptosis Detection ELISA. Estrogen receptor and Bcl-2 mRNA expression was measured by Real-time Quantitative PCR. Results High glucose concentration caused cell proliferation inhibition and apoptosis in cultured human pancreatic beta cells, and these effects were significantly reversed by genistein (P<0.01). Estrogen receptor beta was expressed in the cultured cells, and genistein protection was blocked by ICI-182780 administration as well as Bcl-2 siRNA transfection. Conclusion Phytoestrogen gave protection against high glucose-induced pancreatic cell damage through estrogen receptor beta and Bcl-2 dependent pathways.