ABSTRACT
The title of the article should read:"Role of ß Cell Precursors in the Regeneration of Insulin-Producing Pancreatic ß Cells under the Influence of the Pegylated Form of Glucagon-Like Peptide 1".
ABSTRACT
The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent ß cell precursors (CD45-TER119-CD133+CD49flow) in the pancreas were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1 diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of ß cell precursors and dithizone-stained cells in the pancreas. ß Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect ß cell precursors in diabetic animals. Treatment of a culture of ß cell precursors from mice with diabetes induced the yield of dithizone-stained mononuclears. In conditioned mediums of dithizone-positive cells obtained as a result of differentiation of ß cell precursors from mice with diabetes, insulin was detected after administration of pegGLP-1 (10-7 M) and glucose (3 mmol/liter); the level of insulin increased with increasing glucose concentration (to 20 mmol/liter). The in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10-7 M).
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glucagon-Like Peptide 1/pharmacology , Incretins/pharmacology , Insulin-Secreting Cells/drug effects , Insulin/agonists , Polyethylene Glycols/chemistry , Animals , Antigens, CD/metabolism , Biomarkers/metabolism , Cell Differentiation/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Glucagon-Like Peptide 1/analogs & derivatives , Incretins/chemistry , Injections, Intraperitoneal , Insulin/biosynthesis , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Male , Mice , Mice, Inbred C57BL , Regeneration , StreptozocinABSTRACT
Biological activity of a new pegylated form of an of glucagon-like peptide-1 (GLP-1) analogue pegGLP-1 was studied in C57Bl/6 mice under normal conditions and during modeling of streptozotocin-induced type I diabetes mellitus. pegGLP-1 differs from GLP-1 (7-37) by polyethylene glycol residue covalently bound to His7, Lys26, and Lys34 of the GLP-1 molecule. It was shown that single intragastrical administration of pegGLP-1 induced an increase in GLP-1 level in blood serum of healthy mice. The maximum level of this parameter was observed in 4-8 h. pegGLP-1 elimination half-time was 8.5 h and mean retention time was 15 h. Administration of pegGLP-1 to animals with modeled type I diabetes mellitus was followed by an increase in the levels of GLP-1 and insulin in blood serum, produced a hypoglycemic effect, and improved the parameters of glucose-tolerance test. Biological activity of pegGLP-1 was higher than activity of GLP-1.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glucagon-Like Peptide 1/analogs & derivatives , Glucagon-Like Peptide 1/therapeutic use , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/blood , Glucagon-Like Peptide 1/blood , Hypoglycemic Agents/therapeutic use , Insulin/blood , Insulin/therapeutic use , Male , Mice , Mice, Inbred C57BLABSTRACT
48 full-length Borrelia garinii and Borrelia afzelii from West Siberia and Mongolia ospA gene nucleotide sequences was determined. Four groups of Borrelia garinii were revealed using the analysis of nucleotide sequences. The most variable ospA gene region was demonstrated to be included in region where the antigenic determinants of protein were encoded. High homology level was shown for nucleotide sequences corresponding to isolates of Borrelia afzelii.
Subject(s)
Antigens, Surface/genetics , Bacterial Outer Membrane Proteins/genetics , Bacterial Vaccines/genetics , Borrelia burgdorferi Group/genetics , Genetic Variation , Lipoproteins/genetics , Sequence Homology, Nucleic Acid , Mongolia , SiberiaABSTRACT
The 35 full-length Borrelia burgdorferi sensu lato complex a83/100 gene nucleotide sequences were determined. High level of homology was observed in the nucleotide sequences corresponding to the strains and isolates of Borrelia fzelii. The analysis of the nucleotide sequences revealed two groups of Borrelia garinii. The most variable p83/100 gene region containing species-typical insertions and deletions was demonstrated to be included into the region where the antigenic determinants of protein were encoded. According to the data obtained in this work, the modification of the P83/100 protein structure and immunological properties could be suggested to exist even within species. The results of this work could be used for receiving recombinant P83/100 proteins useful for diagnostic applications.
Subject(s)
Antigens, Bacterial/chemistry , Antigens, Bacterial/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Borrelia burgdorferi Group/classification , Genetic Variation , Amino Acid Sequence , Base Sequence , Borrelia burgdorferi Group/genetics , Borrelia burgdorferi Group/immunology , Genes, Bacterial , Molecular Sequence Data , Mutagenesis, Insertional , Phylogeny , Sequence Analysis, DNA , Sequence DeletionABSTRACT
The content of rheumatoid factor and the levels of IgA, IgM, IgG in patients with different degrees of sensitization to Borrelia garinii antigens were studied. The titer of rheumatoid factor was found to increase in accordance with the growth of the levels of anti-Borrelia antibodies. A rise in the concentration of serum immunoglobulins simultaneously with the development of Borrelia infection was registered. The mechanisms of autoimmunization are discussed, taking into account the known biological properties of the causative agent of Lyme disease.
Subject(s)
Antibodies, Bacterial/blood , Borrelia burgdorferi Group/immunology , Lyme Disease/immunology , Rheumatoid Factor/blood , Adult , Antibodies, Bacterial/biosynthesis , Autoimmunity , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lyme Disease/blood , Middle Aged , Rheumatoid Factor/biosynthesisABSTRACT
The content of rheumatoid factor and serum IgA, IgM and IgG in patients with different degree of sensitization to B. garinii antigens is evaluated. An increase in the titer of rheumatoid factor in patients with a high content of antibodies to Borrelia was established. In addition, an increased concentration of serum immunoglobulins in the presence of Borrelia infection was registered. The mechanisms of autoimmune reactions are discussed, proceeding from the biological properties of the causative agent of Lyme disease.
Subject(s)
Antigens, Bacterial/immunology , Arthritis, Rheumatoid/etiology , Autoantibodies/blood , Borrelia burgdorferi Group/immunology , Lyme Disease/complications , Rheumatoid Factor/blood , Adult , Arthritis, Rheumatoid/blood , Borrelia burgdorferi Group/isolation & purification , Humans , Immunization , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lyme Disease/blood , Lyme Disease/immunology , Middle AgedABSTRACT
The surface of polystyrene plates was studied at different stages of the enzyme immunoassay (EIA) and the passive hemagglutination (PHA) test by the method of scanning electron microscopy in the detection of tick-borne encephalitis (TBE) virus antigen. The study revealed that in the process of EIA larger antigens were washed away from the plate surface. The objects detected on the polystyrene surface were identified as conglomerations of the virions of TBE virus, but whole virions were shown to play no decisive role in EIA. The conclusion was made that, due to some specific features of this method, EIA was more sensitive in reaction with small antigens (individual glycoproteids, their small complexes). And, respectively, the PHA test was more sensitive in reaction with large antigenic complexes (whole virions, their conglomerations, immune complexes).
