Role of β Cell Precursors in the Regeneration of Insulin-Producing Pancreatic β Cells under the Influence of Glucagon-Like Peptide 1

Abstract

The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent β cell precursors (CD45^—TER119^—CD133⁺CD49f^low) 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 β cell precursors and dithizone-stained cells in the pancreas. β Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect β cell precursors in diabetic animals. Treatment of a culture of β 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 β 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).