Low-Molecular-Weight Perorally Active Nerve Growth Factor Mimetic Reduces Manifestations of Diabetic Neuropathy in Wistar Rats

A low-molecular-weight nerve growth factor mimetic, compound GK-2 (bis-(N-monosuccinyl- L-glutamyl-L-lysine)hexamethylenediamide) that previously demonstrated antidiabetic activity in rats with streptozotocin-induced type 2 diabetes mellitus was studied on the model of diabetic neuropathy. It was found that in 8 weeks after diabetes mellitus development, untreated diabetic rats demonstrated impaired tactile sensitivity in von Frey test, while GK-2 therapy (7.5 mg/kg orally for 28 days) restored this parameter. The decrease of tactile sensitivity in diabetic neuropathy closely correlated with the severity of hyperglycemia (r=0.76). Our findings are consistent with the concept on the role of glucose toxicity and nerve growth factor deficiency in the pathogenesis of diabetic neuropathy and attest to feasibility of further studies of nerve growth factor mimetic GK-2 as a potential treatment for diabetes and diabetic neuropathy.