Mutated recombinant human glucagon-like peptide-1 induces differentiation of PC12 cells

Glucagon-like peptide-1 (GLP-1) and its long-acting analogues have neuroprotective and neurotrophic properties and are emerging as potential treatments for neurodegenerative diseases Its short half-life has limited the application of GLP-1 in the clinic. We generated a mutated form of human GLP-1 (mGLP-1) using site-directed mutagenesis and gene recombination techniques, an found that these modifications significantly prolonged the biological half-life of GLP-1 compared wit native GLP-1 (nGLP-1). This study investigated the role of mGLP-1 on inducing PC12 cell differentiation. mGLP-1 induced PC12 cell differentiation with neurite outgrowth and increased the expression of growth-associated protein-43 and neuronal class III ß-tubulin, and significantly increased cyclic adenosine monophosphate level. No significant difference was found between mGLP-1 and nGLP-1. The results indicate that mGLP-1 activates the GLP-1 receptor, induces PC12 cell differentiation, and has neurotrophic effects.