GLP-1 receptor agonists show neuroprotective effects in animal models of diabetes

摘要

Enzyme-resistant receptor agonists of the incretin hormone glucagon-like peptide-1 (GLP-1) have shown positive therapeutic effects in people with type 2 diabetes mellitus (T2DM). T2DM has detrimental effects on brain function and impairment of cognition and memory formation has been described. One of the underlying mechanisms is most likely insulin de-sensitization in the brain, as insulin improves cognitive impairments and enhances learning. Treatment with GLP-1 receptor agonists improves memory formation and impairment of synaptic plasticity observed in animal models of diabetes-obesity. Furthermore, it has been shown that diabetes impairs growth factor signalling in the brain and reduces energy utilization in the cortex. Inflammation and apoptotic signalling was also increased. Treatment with GLP-1 receptor agonists improved neuronal growth and repair and reduced inflammation and apoptosis as well as oxidative stress. In comparison with the diabetes drug metformin, GLP-1 receptor agonists were able to improve glycemic control and reverse brain impairments, whereas metformin only normalized blood glucose levels. Clinical studies in non-diabetic patients with neuro-degenerative disorders showed neuroprotective effects following administration with GLP-1 receptor agonists, demonstrating that neuroprotective effects are independent of blood glucose levels.