TY - JOUR

T1 - GLP-1 receptor agonists show neuroprotective effects in animal models of diabetes

AU - Gault, Victor A.

AU - Hölscher, Christian

N1 - This is the author’s version of a work that was accepted for publication in Peptides. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Peptides, 100, 2018 DOI: 10.1016/j.peptides.2017.11.017

PY - 2018/2

Y1 - 2018/2

N2 - 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 neurodegenerative disorders showed neuroprotective effects following administration with GLP-1 receptor agonists, demonstrating that neuroprotective effects are independent of blood glucose levels.

AB - 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 neurodegenerative disorders showed neuroprotective effects following administration with GLP-1 receptor agonists, demonstrating that neuroprotective effects are independent of blood glucose levels.

KW - GLP-1

KW - GIP

KW - Brain

KW - Neurons

KW - Growth factors

KW - Neurodegeneration

KW - Inflammation

U2 - 10.1016/j.peptides.2017.11.017

DO - 10.1016/j.peptides.2017.11.017

M3 - Journal article

VL - 100

SP - 101

EP - 107

JO - Peptides

JF - Peptides

SN - 0196-9781

ER -