Brain Signaling Systems in the Type 2 Diabetes and Metabolic Syndrome: Promising Target to Treat and Prevent These Diseases

Abstract

The changes in the brain signaling systems play an important role in etiology and pathogenesis of Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), being a possible cause of these diseases. Therefore, their restoration at the early stages of T2DM and MS can be regarded as a promising way to treat and prevent these diseases and their complications. The data on the functional state of the brain signaling systems regulated by insulin, IGF-1, leptin, dopamine, serotonin, melanocortins and glucagon-like peptide-1, in T2DM and MS, are analyzed. The pharmacological approaches to restoration of these systems and improvement of insulin sensitivity, energy expenditure, lipid metabolism, and to prevent diabetic complications are discussed.

Currently, more than 30% of the populations worldwide are overweight and have metabolic dysfunctions that without the appropriate treatment would go over to severe Type 2 diabetes mellitus (T2DM). At the early stages of T2DM significant changes occur in the brain signaling systems, resulting in the impairment of metabolism and the functions of nervous, cardiovascular and the other systems. Restoration of the brain signaling is regarded as a promising way to treat and prevent diabetic pathology. In the review the changes in the brain signaling systems in T2DM and the pharmacological approaches to their restoration are discussed.

Keywords::

• brain
• bromocryptine
• diabetes mellitus
• insulin
• leptin
• melanocortin
• metabolic syndrome
• neurodegeneration
• signaling systems
• treatment

Author contributions

AO Shpakov prepared the sections ‘Introduction’, ‘Brain insulin and IGF-1 signaling’, ‘Leptin signaling system’, ‘Dopamine signaling system’, ‘Serotonin signaling system’ and ‘Conclusions and perspectives’. KV Derkach prepared the sections ‘Melanocortin signaling system’ and ‘Glucagon-like peptide-1 and its signaling’, and the figures. LM Berstein prepared the sections ‘Introduction’, ‘Brain insulin and IGF-1 signaling’ and ‘Leptin signaling system’. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by the Russian Science Foundation (project No 14-15-00413). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Russian Science Foundation (project No 14-15-00413). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.