Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets

  • Thierry CoppolaEmail author
  • Sophie Beraud-Dufour
  • Patricia Lebrun
  • Nicolas BlondeauEmail author
Review Paper


Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, incidence of stroke in the presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrants the need to integrate this comorbidity in preclinical studies of brain ischemia to develop novel therapeutic approaches. Therefore, a better understanding of the commonalties involved in the course of both diseases would offer the promise of discovering novel neuroprotective pathways that would be more appropriated to clinical scenarios. In this article, we will review the relevant mechanisms that have been identified as common traits of both pathologies and that could be, to our knowledge, potential targets in both pathologies.


Hyperglycemia Glucolipotoxicity Comorbidity Tolerance to brain ischemia Signaling pathways 


ACE inhibitors

Angiotensin converting enzyme inhibitors


American diabetes association


Serine–threonine kinase


Angiotensin II receptor blockers


Activating transcription factor 3


Adenosine triphosphate


Ca2+/calmodulin kinase


CaM kinase kinase


Cyclic adenosine monophosphate


Central nervous system


C-AMP response element-binding protein


C-reactive protein


Dipeptidyl peptidase-4


Free fatty acid


Glucagon-like peptide-1


Hemoglobin A1c


High-density lipoproteins


Inducible cAMP early repressor




c-Jun N-terminal kinases


Low-density lipoproteins


Nerve growth factor






Protein kinase A


Protein kinase B


Protein kinase Cdelta


Reactive oxygen species


Sodium-glucose co-transporter-2


Stroke therapy academic industry roundtable


Tumor necrosis factor


Veterans affairs diabetes trial


Very low-density lipoproteins



The authors thank all their past and present team members and collaborators who have contributed to the data discussed in the review. We would like to express our gratitude to Drs. Heurteaux and Mazzela for their cordial support, valuable information, and guidance, which helped us in completing this review.


This work was funded by the Centre National de la Recherche Scientifique - CNRS.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Université Côte d’Azur, CNRS, IPMCValbonneFrance

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