Anti-diabetic drugs against stroke

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Researchers at KI SÖS have shown that a group of anti-diabetic drugs can protect the brain from stroke independently of their anti-diabetic properties. The findings might open up for new avenues aiming to develop new pharmacological treatments against neurological disorders in diabetic and non-diabetic patients.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are clinically used drugs for the treatment of type 2 diabetes. They preserve the high concentration of hormone glucagon-like peptide 1 (GLP-1) in the blood, which in turn enhances insulin production and reduces blood glucose in diabetic patients.

Dr. Patrone’s research group has previously shown that DPP-4 inhibitors can also reduce brain injury after stroke (Darsalia et al, Diabetes 2013). This protective effect was thought to occur via the regulation of GLP-1, although a direct proof this was absent.  In the current study published in Diabetes, Obesity and Metabolism1, Dr. Vladimer Darsalia and coauthors have been able to show that the anti-stroke efficacy mediated by DPP-4 inhibitors is completely independent of GLP-1.

The findings open up new avenues aiming to unravel the molecular mechanisms of DPP-4 inhibitors and thus to exploit the therapeutic potential of these group of drugs, against neurological disorders in diabetic and non-diabetic patients.

This study is a result of a collaborative effort of researchers at Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset with Boehringer Ingelheim Pharma.

The work was conceived and directed by Associate Professor Cesare Patrone and Dr Vladimer Darsalia. Funders of the study were: European Foundation for the Study of Diabetes, Diabetesfonden, the Swedish Heart and Lung Foundation, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Diabetes Research & Wellness Foundation and by the foundations: Magnus Bergvall, Åhlén, STROKE Riksförbundet, Tornspiran, Gamla Tjänarinnor, O. E. och Edla Johanssons vetenskapliga stiftelse, Syskonen Svensson and by the Fighting Stroke Project (Uppdrag Besegra Stroke) supported by the Swedish Heart and Lung foundation and by the Karolinska Institutet.

Gliptins-mediated neuroprotection against stroke requires chronic pre-treatment and is glucagon-like peptide-1 receptor independent.
Darsalia V, Larsson M, Lietzau G, Nathanson D, Nyström T, Klein T, Patrone C.
Diabetes Obes Metab. 2016 Feb 5. doi: 10.1111/dom.12641. [Epub ahead of print] PMID:26847506