Noopept Normalizes Parameters of the Incretin System in Rats with Experimental Diabetes

Abstract

Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations.

Exenatide upregulates gene expression of glucagon‐like peptide‐1 receptor and nerve growth factor in streptozotocin/nicotinamide‐induced diabetic mice

“…Exenatide treatment upregulated GLP-1 receptor gene expression as 2.010 fold changes. Our results confirm previous data [17,45] and might explain the protective role of exenatide in enhancing insulin secretion. So as it is suggested by During et al…”

“…The content of GLP‐1 decreases multiple folds in STZ‐receiving rats . In our study, hippocampal gene expression of GLP‐1 receptor downregulated as 4503 fold change in type 2 diabetic mice as compared to control group.…”

“…GLP-1 and exendin-4 increase cell mass by enhancing proliferation and neogenesis in diabetic models, such as partially pancreatectomized and STZ-treated rats [44]. Ostrovskaya et al [45] had previously postulated that STZ decreased the concentrations of incretin GLP-1 and insulin in the blood of rats. The content of GLP-1 decreases multiple folds in STZ-receiving rats [45].…”

“…Ostrovskaya et al [45] had previously postulated that STZ decreased the concentrations of incretin GLP-1 and insulin in the blood of rats. The content of GLP-1 decreases multiple folds in STZ-receiving rats [45]. In our study, hippocampal gene expression of GLP-1 receptor downregulated as 4503 fold change in type 2 diabetic mice as compared to control group.…”

Nootropic dipeptide, Noopept can modulate hyperalgesia by effecting on spinal microglia dependent Brain Derived Neurotropic Factor (BDNF) and pro-BDNF expression and apoptosis during persistent inflammation

“…Although there are considerable studies on the anti-inflammatory effect of Noopept [28,61], the current study stated the novel dipeptide anti-hyperalgesic and anti-inflammatory effects were mediated via inhibition of microglia activity and apoptosis. Ostrovskaya et al showed that Noopept, through normalizing incretin system parameters, had an anti-apoptotic effect on pancreatic β cells in the context of experimental Diabetes [63], and in another study they indicated neuroprotective effects [64]. Moreover, the effects reported in this paper in response to Noopept were significantly more effective than those reported for minocycline administration in the CFA-inflamed groups, which indicates that there are other pathways involved in Noopept anti-inflammatory effects which need to…”