Dose-Dependent Effect of Nerve Growth Factor Mimetic GK-2 in a Wistar Rat Diabetes Model

Experimental results for the new nerve growth factor (NGF) mimetic GK-2 [bis-(N-monosuccinyl-L-glutamyl-L-lysine)hexamethylenediamide] administered perorally toWistar rats in a streptozotocin-induced type 2 diabetes mellitus model are reported. The antihyperglycemic activity of GK-2 was determined in a dose range from 1 to 10 mg/kg. The most pronounced effect was observed at doses of 2.5 and 5 mg/kg. GK-2 was also found to reduce the severity of polydipsia and polyphagia and to produce a positive effect on the body-weight dynamics of diabetic animals. The dose dependence of GK-2 effects was described by a bell-shaped curve typical of regulatory peptides with various chemical structures. The ten-fold greater width of the dose–activity curve of the drug observed in this work combined with its high safety suggests that a satisfactory therapeutic index for GK-2 as a potential antidiabetic drug for peroral administration can be expected.