期刊
DIABETES OBESITY & METABOLISM
卷 18, 期 5, 页码 537-541出版社
WILEY
DOI: 10.1111/dom.12641
关键词
DPP-4 inhibitors; gliptins; GLP-1; linagliptin; stroke; type 2 diabetes
资金
- Boehringer Ingelheim Pharma GmbH Co. KG
- European Foundation for the Study of Diabetes, Diabetesfonden
- Swedish Heart and Lung Foundation
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Diabetes Research
- Wellness Foundation
- foundation O. E. och Edla Johanssons
- Magnus Bergvalls Stiftelse
- Ahlen-stiftelsen
- STROKE Riksforbundet
- Torn-spiran
- Stiftelsen for Gamla Tjanarinnor
- Stiftelsen syskonen Svenssons stiftelse for medicinsk forskning
- Fighting Stroke Project (Uppdrag Besegra Stroke)
- Karolinska Institutet
Gliptins are anti-type 2 diabetes (T2D) drugs that regulate 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 for reducing brain damage in patients with T2D and high risk of stroke. It is not known, however, whether acute gliptin treatment after stroke (mimicking a post-hospitalization treatment) is neuroprotective or whether gliptin-mediated neuroprotection occurs via GLP-1-receptor (GLP-1R) activation. To answer these two questions, wild-type and glp-1r(-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50 mg/kg intravenously), at MCAO time or chronically (10 mg/kg orally) 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 dipeptidyl peptidase-4 activity were also measured. The results show that the linagliptin-mediated neuroprotection against stroke requires chronic pretreatment and does not occur via GLP-1R. The findings provide essential new knowledge with regard to the potential clinical use of gliptins against stroke, as well as a strong impetus to identify gliptin-mediated neuroprotective mechanisms.
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