**7. Conclusion**

Reversible changes occur in the early phase of hyperglycemic injury that might be pharmacologically targetable. Blocking the high glucose-induced mitochondrial superoxide production represents the major goal in endothelial cells, but it does not provide a drug target that can be directly assessed [169, 170]. The involvement of mitochondria in the pathogenesis of various diseases intensified the interest in druggable targets and promoted selective delivery of compounds to the mitochondria [146]. Normalization of the mitochondrial membrane potential or administration of mitochondria-specific free radical scavengers reverses the adverse effects of hyperglycemia and may present experimental therapeutic approaches in diabetes [16, 38, 100]. Early administration of mitochondrial antioxidants or drugs that restore the mitochondrial metabolism is expected to prevent the later changes that occur in diabetes.

The later stages of hyperglycemic injury also include morphological changes and impaired assembly of the respiratory complexes that necessitate different treatment strategies. Mitochondrial fusion promoting drugs might represent promising approaches in this phase of diabetes complications but their efficacy has not been tested in diabetes [152, 153]. Alternatively, stimulation of the endothelial progenitor cells to help replace the senescent endothelial cells may prove beneficial in diabetes [126].

Altogether, advancement in our understanding of glucose-induced cellular and mitochondrial damage and identification of new drug targets are expected to provide novel strategies in diabetes treatment.
