A Recombinant GLP-1-Derived Peptide with a C-Terminal Polyleucine Extension Exhibits Incretin-Like Activity in MIN6 Cells

Glucagon-like peptide-1 receptor agonists are widely used for treating type 2 diabetes mellitus and obesity, but new peptide variants and scalable production platforms remain needed. Here, we designed and recombinantly produced M-GLP-1-8L, a GLP-1-derived peptide containing an N-terminal methionine and a C-terminal polyleucine extension. The peptide was expressed in Escherichia coli, purified, and evaluated in MIN6 pancreatic β-cells. RT-qPCR confirmed expression of Glp1r and Dpp4, supporting the suitability of the model. M-GLP-1-8L significantly increased insulin secretion under additional glucose loading compared with untreated cells; its effect was weaker than semaglutide but comparable to M-GLP-1. In the MTT assay, M-GLP-1-8L showed a non-significant tendency to increase metabolically active cell number. Exploratory structural modeling revealed no obvious incompatibility with GLP-1 receptor interaction. These results support the feasibility of recombinant GLP-1-derived peptide engineering.