RESUMO
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".
RESUMO
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).
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Incretinas/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/agonistas , Polietilenoglicóis/química , Animais , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Incretinas/química , Injeções Intraperitoneais , Insulina/biossíntese , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração , EstreptozocinaRESUMO
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.
