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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
  • 60 Downloads

Abstract

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.

Keywords

Hyperglycemia Glucolipotoxicity Comorbidity Tolerance to brain ischemia Signaling pathways 

Abbreviations

ACE inhibitors

Angiotensin converting enzyme inhibitors

ADA

American diabetes association

Akt

Serine–threonine kinase

ARBs

Angiotensin II receptor blockers

ATF3

Activating transcription factor 3

ATP

Adenosine triphosphate

CamK

Ca2+/calmodulin kinase

CaMKK

CaM kinase kinase

cAMP

Cyclic adenosine monophosphate

CNS

Central nervous system

CREB

C-AMP response element-binding protein

CRP

C-reactive protein

DPP-4

Dipeptidyl peptidase-4

FFA

Free fatty acid

GLP-1

Glucagon-like peptide-1

HbA1c

Hemoglobin A1c

HDL

High-density lipoproteins

ICER

Inducible cAMP early repressor

IL1-β

Interleukin1-beta

JNKs

c-Jun N-terminal kinases

LDL

Low-density lipoproteins

NGF

Nerve growth factor

NMDA

N-methyl-D-aspartate

PDE

Phosphodiesterase

PKA

Protein kinase A

PKB

Protein kinase B

PKCδ

Protein kinase Cdelta

ROS

Reactive oxygen species

SGLT-2

Sodium-glucose co-transporter-2

STAIR

Stroke therapy academic industry roundtable

TNF

Tumor necrosis factor

VADT

Veterans affairs diabetes trial

VLDL

Very low-density lipoproteins

Notes

Acknowledgements

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.

Funding

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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