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Liraglutide treatment sustains neuronal glycolysis and prevents hyperinsulinemia‐induced neuronal senescence
Author(s) -
Chow HeiMan,
Herrup Karl
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044992
Subject(s) - liraglutide , hyperinsulinemia , senescence , insulin , endocrinology , medicine , neurodegeneration , insulin resistance , prediabetes , diabetes mellitus , neuron , pharmacology , biology , neuroscience , type 2 diabetes , disease
Abstract Background We previously reported hyperinsulinemia during prediabetes could lead to neuronal insulin resistance and cell cycle‐induced senescence. These findings offer a direct connection between peripheral hyperinsulinemia, as found in prediabetes, age‐related neurodegeneration and cognitive decline. Here we attempted to investigate if Liraglutide‐the FDA approved diabetes drug‐can prevent insulin‐induced senescence in neurons. Method Toxicity and optimal treatment strategies were first performed in primary neuronal culture (n=9). After that, optimal dosages of Liraglutide was co‐treated with long‐lasting insulin glargine for 72 hours. A series of post‐treatment biochemical, immunocytochemistry and electrophysiology analyses were performed. Result Liraglutide treatment did not reveal toxicity to neurons even at micro‐molar dosage. Liraglutide co‐treatment with insulin substantially preserved glycolysis capacity in primary neuronal cultures. Initiation of drug treatment prior or simultaneously with insulin revealed almost equal protective on neurite morphology; synaptic protein abundance and distribution; electrophysiology properties and be able to suppress cell‐cycle associated senescence. Conclusion Liraglutide effectively prevents the entire range of structural and functional abnormalities in neurons induced by chronic exposure of insulin.