Effect of chronic exposure to ketohexoses on pancreatic β-cell function in INS-1 rat insulinoma cells.

Glucotoxicity, impaired insulin secretion, suppression of insulin gene expression and apoptosis, in pancreatic β-cells caused by chronic hyperglycemia is a key component of the pathogenesis of type 2 diabetes. Recently, it has been reported that rare sugar D-allulose has antihyperglycemic and antihyperlipidemic effects in diabetic rats. However, the direct effects of rare sugars including D-allulose on pancreatic β-cell function are unclear. In this study, we investigated whether chronic exposure to ketohexoses causes glucotoxicity, suppression of insulin gene expression and apoptosis, in INS-1 rat pancreatic insulinoma cells. D-Fructose, D-tagatose, L-allulose, and L-sorbose treatment for 1-week reduced insulin gene expression, whereas D-allulose, D-sorbose, L-fructose, and L-tagatose did not. All ketohexoses were transported into INS-1 cells, but were not metabolized. In addition, the ketohexoses did not induce apoptosis and did not affect glucose metabolism. These results suggest that long-term administration of D-allulose, D-sorbose, L-fructose and L-tagatose does not affect pancreatic β-cell function.