Gliptins‐mediated neuroprotection against stroke requires chronic pre‐treatment and is glucagon‐like peptide‐1 receptor independent

Abstract Gliptins are anti‐type 2 diabetic (T2D) drugs regulating glycaemia by preventing endogenous glucagon‐like peptide‐1 (GLP‐1) degradation. Chronically administered gliptins before experimental stroke can also induce neuroprotection and this effect is potentially relevant to reduce brain damage in high stroke‐risk T2D patients. However, it is unknown: 1) whether acute gliptins‐treatment after stroke (mimicking a post‐hospitalization treatment) is neuroprotective 2) whether gliptins‐mediated neuroprotection occurs via GLP‐1‐receptor (GLP‐1R) activation. To answer these two questions, wt and glp‐1r−/− mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50mg/Kg intravenously), at MCAO time or chronically (10mg/Kg per‐oral) for 4 weeks before and 3 weeks after MCAO. Neuroprotection was assessed by stroke volume measurement and quantification of NeuN‐positive surviving neurons. Plasma/brain GLP‐1 levels and DPP‐4 activity were also measured. The results show that the Linagliptin‐mediated neuroprotection against stroke requires chronic pretreatment and it does not occur via GLP‐1R. The findings provide new essential knowledge for the potential clinical use of gliptins against stroke as well as a strong impetus aiming to identify gliptin‐mediated neuroprotective mechanisms.
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: LETTER TO THE EDITOR Source Type: research