Introduction: The normalization of cellular glucose assimilation is the basic aim of metabolic therapy in type 2 diabetes mellitus (T2DM). It requires parallel changes in the process of cellular glucose transport (CGT). Therefore the level of CGT could be regarded as a therapeutic target for oral hypoglycemic drugs in T2DM. To explore this hypothesis, CGT levels before and after sulfonylurea therapy were investigated. Peripheral blood lymphocytes were used as a cell model for testing CGT.
Materials and methods: CGT was assessed by experimental in vitro tests allowing timed comparative observation of the transport process during the incubation of lymphocytes with 2-[(3)H(G)] glucose under basal conditions and after the addition of sulfonylurea or sulfonylurea plus insulin. The incubation tests were performed at baseline in 28 persons with newly diagnosed, therapy-naive T2DM and in 20 control subjects. In the diabetic patients the tests for CGT were repeated after 3 months of sulfonylurea therapy. The level of glucotransporter 4 (GLUT4) expression was also assessed by flow cytometry before and after the therapy.
Results: Before treatment, CGT was significantly lower in the subjects with T2DM. The cells responded to the addition of sulfonylurea by a moderate increase in CGT. This response was augmented by the addition of insulin to sulfonylurea in the culture medium.
Conclusions: The three-month therapy with sulfonylurea resulted in a significant increase in CGT in all types of culture tests. This sulfonylurea-related improvement in CGT was associated with a near normalization of GLUT4 expression in the cells.