\r\nShe presents the research of group of V.V. Zakusov Institute of Pharmacology, Moscow, Russia. This group is working with the problem of diabetes accompanying by behavioral disorders and their correction with original peptide mimetics of NGF and BDNF designed in this institute\r\n
Original dimeric dipeptide mimetic GK-2 (hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine) was synthesized based on the structure of β-turn of NGF loop 4 at the V.V. Zakusov Institute of Pharmacology (Seredenin S., Gudasheva T., RF patent 2410392). The purpose of this study was to investigate whether it affects the effects of diabetogenic toxin, streptozotocine (STZ). Experiments were carried out on C57/Bl6 mice divided into 4 groups: passive control treated with saline; active control treated with STZ 100 mg/kg; animals treated with GK-2 0.5 mg/kg i.p. for 14 days before and 14 days after STZ; animals treated with 5 mg/kg of GK-2 p.o. at the same schedule. Persentage of animals able to find the invisible platform in Morris water maze and the immobility duration in Porsolt test have been estimated. The content of MDA as a sign of oxidative stress was measured in plasma. GK-2 was shown to be able to overcome hyperglycemia, body weight loss, to diminish MDA accumulation caused by STZ. While STZ diminished the % of mice able to find the platform to 9 % comparing to 14% in passive control, GK-2 treated mice demonstrated the figures as high as 27.3 and 50% for i.p and p.o routes of administration correspondingly. GK-2 ameliorated also the signs of depression. Therefore, GK-2 was shown to antagonize main effects of STZ; these effects lasted after discontinuation of treatment.
Ostrovskaya Rita U. – Professor. D Sc., M.D., Main Researcher of Psychopharmacology Department of Zakusov State Institute of Pharmacology. Author of more than 250 publications, 20 patents. Hirsh index according Scopus 15, Research Gate index 37.34
Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) revealed wide spectrum of neuroprotective effects (Seredenin et al, Patent USA 5.439.930; Gudasheva et al., Eur. J. Med. Chem. 1996, 31, 151 - 157). One of mechanism underlying this neuroprotection is the increase of NGF and BDNF expression in hippocampus and hypothalamus. Features of neurons and pancreatic beta-cells similarity (Scharfmann. Horm. Metab. Res. 1997, 29, 294—296) as well as data on neurotrophines insufficiency in diabetes (Krabbe et al., Diabetologia. 2007, 50, 431-438) prompted us to study the effects of Noopept 0.5 mg/kg i.p. for 14 days, before streptocotozine 40 mg/kg i.p. on rats. Besides of well-known STZ ability to produce hyperglycemia and weight loss, we revealed pronounced decrease of NGF and BDNF content in pancreatic and hepatic tissues. Noopept was firstly shown to ameliorate hyperglycemia, weight loss as well as to overcome NGF and BDNF deficits in these organs. Recent study of Vahitova et al. (Acta Naturae 2016, 8, 1, 90-98) revealed Noopept ability to increase the content of HIF-1. Involvement of HIF-1 deficiency in pathogenesis of diabetes combined with HIF ability to increase neurotrophines expression (Girgis et al. Trends in Endocrinology and Metabolism, 2012, 23, 372-380) allow to consider HIF-positve effects of Noopept as one of the mechanism underlying above-listed anti-diabetic effect of Noopept.rnrn