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,and found that these modifications significantly prolonged the biological half-life of GLP-1 compared with 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-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.
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