Pancragen

We examined two groups of older persons: 30 healthy and 33 patients with type 2 diabetes mellitius. Nocturnal melatonin production was significantly reduced by 70% in patients with DM2 compared to healthy individuals of the corresponding age. In patients with DM2, pancragen significantly decreased glucose level on an empty stomach and in standard glucose tolerance test and reduced plasma concentrations of insulin and insulin resistance index. In patients receiving no pancragen, no changes in carbohydrate metabolism indices were observed. Thus, disturbances in the melatonin-producing function of the pineal gland in elderly individuals contribute to the development of insulin resistance. Administration of the tetrapeptide pancragen is a promising approach to the correction of insulin resistance in elderly individuals.

Expression of differentiation markers was found to be reduced during ageing of pancreatic cells. Tetrapeptide pancragen stimulates the expression of differentiation factors of acinar (Pdx1, Ptfla) and islet of Langerhans (Pdx1, Pax6, Pax4, Foxa2, NKx2.2) cells in "young" and " aged" cultures. Differentiation of acinar and islet pancreatic cells induced by pancragen can be a mechanism underlying its anti-diabetic and anti-inflammatory effects. Thus, transcription factors that regulate differentiation of pancreatic cells are a pharmacological target for pancragen, which allows considering it as an effective tool in the treatment of diabetes mellitus and pancreatitis.

The aim of the investigation was comparative study of the influence tetrapeptide Pancragen (St. Petersburg Institute of Bioregulation and Gerontology, St. Petersburg) on hormonal function of the pancreas compared to the effect of widely used hypoglycemic drug - glimepiride. The investigation involved 9 old (20-25 years) clinically healthy rhesus monkey females (Macaca mulatta). Five of them were injected with Pancragen (0,05 mg/animal per day during 10 days, intramuscularly) for 10 days; 4 animals received glimepiride (4 mg/animal per day during 10 days, per os). Blood samples were taken from all the animals with subsequent analysis of glucose, insulin and C peptide levels; the manipulation was performed before administration of the drugs, on the background of their administration and after their withdrawal in basal conditions, as well as during glucose tolerance testing. Pancragen and glimepiride administration induced the decrease of blood glucose basal levels in both groups of old monkeys. Pancragen also normalized insulin and C peptide levels suggesting its recovering effect on the disturbed tolerance to glucose in old animals. At the same time, glimepiride administration led to a more expressed and delayed hypoglycemic effect and C peptide secretion stimulation without any significant effect on insulin secretion. The data suggest that Pancragen is effective and safe for correction of age-related imbalance of endocrine pancreatic function, and can be used for elderly patient with disturbed glucose tolerance.

Significant increase of the elderly in the demographic structure of a modern society is one of the main reasons for increase in the number of patients with diabetes type 2 and impaired glucose tolerance. The purpose of this research was to study impact of Pancragen (tetrapeptide Lys-Glu-Asp-Trp) on endocrine function of the pancreas of non-human primates, female rhesus monkeys, and to elucidate the possibil- ity of its use for correction age-related dysfunction of pancreatic islet apparatus. In old animals after the glucose administration (standard dose) in control period, a reduced glucose "disappearance" rate and a higher values of insulin and C-peptide peaks (5 and 15 min after the glucose injection) were observed in comparison with young animals in similar experiments. Pancragen administration (50 μg/animal per day during 10 days, intramuscularly) to old monkeys caused markedly increased the glucose "disappear- ance" rate, normalized the plasma insulin and C-peptide dynamics in response to glucose administration. The recovering effect of Pancragen on the function of the pancreas partially remained 3 weeks after discontinuation of the drug. Thus, Pancragen is a promising factor for restoring the age-related endocrine dysfunction of primates.