Инсулин-позитивные клетки печени и экзокринной части поджелудочной железы у животных с экспериментальным сахарным диабетом

Aim. To compare the number of insulin+ cells in the liver and exocrine part of the pancreas with the type of experimental diabetes, blood glycose and glycated hemoglobin (HbA1c) level and with the number of Pdx1+ cells. Materials and methods. The experiment was carried out on 25 male Wistar rats (weighting (303.0 ± 25.3) g) that were divided into 3 groups: The first group consisted of intact animals, the second had animals with experimental diabetes type 1, and the third with animals with experimental diabetes type 2. Biochemical, immunohistochemical, ELISA methods and statistical analysis were used. Results. Insulin+ and Pdx1+ cells of rats with experimental diabetes were found in the liver and exocrine part of pancreas. The highest number of insulin+ cells in the liver was detected in type 2 diabetes (T2D). A strong positive correlation between the number of insulin+ cells in the liver and level of glycosylated hemoglobin in theblood was revealed in both type 1 and type 2 diabetes. Conclusion. Insulin+ cells are detected in the liver and acinar part of pancreas of both intact rats and rats with experimental diabetes. Group with T2D is characterized by the highest number of insulin+ cells in the liver compared with type 1 diabetes (T1D). The localization of insulin+ cells in the liver changes depending on the type of diabetes. In T2D insulin+ cells are located in all parts of liver acini, meanwhile in animals with T1D such cells are mainly detected in the periportal area. The expression of Pdx1+ in acinar cells of pancreas and liver cells is likely a mechanism for their reprogramming into insulin+ cells in experimental diabetes mellitus. © 2020 Siberian State Medical University. All rights reserved.This work was financially supported by the Russian Science Foundation, grant No. 16-1500039-P and the budget project No. АААА-А18-118020590108-7 of the Institute of Immunology and Physiology, UB RAS

Accelerated Generation of Extra-Islet Insulin-Producing Cells in Diabetic Rats, Treated with Sodium Phthalhydrazide

β-cells dysfunction plays an important role in the pathogenesis of type 2 diabetes (T2D), partially may be compensated by the generation of extra-islet insulin-producing cells (IPCs) in pancreatic acini and ducts. Pdx1 expression and inflammatory level are suggested to be involved in the generation of extra-islet IPCs, but the exact reasons and mechanisms of it are unclear. Macrophages are key inflammatory mediators in T2D. We studied changes in mass and characteristics of extra-islet IPCs in rats with a streptozotocin-nicotinamide model of T2D and after i.m. administration of 20 daily doses of 2 mg/kg b.w. sodium aminophthalhydrazide (APH). Previously, we found that APH modulates macrophage production and increases the proliferative activity of pancreatic β-cells. Expressions of insulin and Pdx1, as well as F4/80 (macrophage marker), were detected at the protein level by immunohistochemistry analysis, the concentration of pro- and anti-inflammatory cytokines in blood and pancreas—by ELISA. Diabetic rats treated with APH showed an increasing mass of extra-islet IPCs and the content of insulin in them. The presence of Pdx1+ cells in the exocrine pancreas also increased. F4/80+ cell reduction was accompanied by increasing TGF-β1 content. Interestingly, during the development of diabetes, the mass of β-cells decreased faster than the mass of extra-islet IPCs, and extra-islet IPCs reacted to experimental T2D differently depending on their acinar or ductal location

Antihyperglycemic activity of colostrum peptides

Peptides of plant and animal origin have good anti-diabetic prospects. The research objective was to use bovine colostrum peptides to reduce hyperglycemia in diabetic rats. Bovine colostrum peptides were obtained by trypsin hydrolysis of colostrum proteins with preliminary extraction of triglycerides. The study involved four groups of Wistar rats with seven animals per group. Group 1 served as control; group 2 received 300 mg/kg of trypsin hydrolysate of bovine colostrum as part of their daily diet for 30 days. Groups 3 and 4 had diabetes mellitus caused by intraperitoneal injections of 110 mg/kg of nicotinamide and 65 mg/kg of streptozotocin. Group 4 also received 300 mg/kg trypsin hydrolysate of bovine colostrum intragastrically five times a week for 30 days. Three peptides were isolated from the trypsin hydrolysate of bovine colostrum and tested for the sequence of amino acids and molecular weight. Their identification involved the Protein NCBI database, followed by 2D and 3D modeling, which revealed their chemical profile, pharmacological properties, and antioxidant activity. The diabetic rats treated with colostrum peptides had lower glucose, glycated hemoglobin, malondialdehyde, and catalase activity but a higher content of glutathione in the blood. Their leukocytes and erythrocytes also demonstrated less deviation from the standard. The antioxidant effect of colostrum protein hydrolysate depended on a peptide with the amino acid sequence of SQKKKNCPNGTRIRVPGPGP and a mass of 8.4 kDa. Colostrum peptides reduced hyperglycemia and oxidative stress in diabetic rats. The research revealed good prospects for isolating individual colostrum peptides to be tested for antidiabetic properties

Protective Effect of Betulin on Streptozotocin–Nicotinamide-Induced Diabetes in Female Rats

Type 2 diabetes is characterized by hyperglycemia and a relative loss of β–cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin–nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α–amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA–IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β–cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes