Low molecular weight NGF mimetic GK-2 normalizes the parameters of glucose and lipid metabolism and exhibits a hepatoprotective effect on a prediabetes model in obese Wistar rats.

Abstract

Signs of metabolic syndrome and prediabetes preceding type 2 diabetes are modelled in an experiment using a high-fat diet (HFD). The aim of this work was to study the effect of a low molecular weight systemically active nerve growth factor mimetic, compound GK-2 (hexamethylenediamide bis[N-monosuccinyl-L-glutamyl-L-lysine]), on indicators of abdominal obesity, basal blood glucose level, glucose tolerance, cholesterol and triglyceride blood levels, as well as the morphological structure of the liver in male Wistar rats fed a HFD. Rats were divided into three groups: one of them received standard food (control) and two others were fed a HFD containing 45% fat, 35% carbohydrates and 20% protein, with a total caloric value of 516 kcal/100 g, over 12 weeks. Starting from the ninth week, for the next 4 weeks, one of the HFD groups was treated orally with saline whilst the other group was treated orally with GK-2 at a dose of 5 mg/kg. GK-2 was found to reduce the basal glycaemia level and improve glucose tolerance, as well as to reduce the blood level of cholesterol by 30% and that of triglycerides by 28% in comparison with the saline-treated HFD animals. GK-2 reduced the degree of abdominal obesity to the level of the healthy animals and eliminated morphological abnormalities in the liver caused by the HFD. The results of the study determine the feasibility of further GK-2 research as a potential agent for prediabetes treatment.