The role of ketonemia induced by sodium-glucose cotransporter 2 inhibitors: from the energy exchange to cardioprotection


DOI: https://dx.doi.org/10.18565/therapy.2021.10.94-109

Salukhov V.V., Khalimov Yu.Sh., Cherkashin D.V., Kadin D.V.

S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia, Saint Petersburg
Abstract. Ketonemia is one of the factors presumably responsible for improving cardiovascular outcomes in studies of SGLT2 inhibitors. The purpose of this review is to compare traditional and modern ideas about the features of normal myocardial energy metabolism and pathology, the possibilities of metabolic support of failing heart, the physiology of ketogenesis, the role of ketone bodies in the body and the effect of ketones on various pathological processes. The role of substrate shifts of oxidative phosphorylation in the heart failure development is analyzed. The mechanisms of action of existing drugs to optimize the metabolism of damaged myocardium are discussed. The main stages of ketone bodies metabolism are presented, with their effect on energy metabolism and the functional state of a healthy and failing heart being highlighted. Recent advances in the study of the regulatory functions of ketones at the systemic and cellular levels are disclosed, taking into account possible receptor, epigenetic and other «noncanonical» effects. A brief description of the role of ketone bodies in brain metabolism is given, with contemporary opinions concerning the mechanisms of ketone-mediated neuroprotection to be discussed. Actual data about the mechanisms of influence of SGLT2 inhibitors on the course of cardiovascular diseases and the characteristics of the drug-induced ketonemia are presented.
Keywords: sodium-glucose cotransporter 2 inhibitors, ketone bodies, energy metabolism, heart failure
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About the Autors

Vladimir V. Salukhov, MD, associate professor, head of the 1st Department and clinic (advanced therapy for doctors) named after academician N.S. Molchanov, S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia. Address: 194044, Saint Petersburg, 6Zh Akademika Lebedeva Str. Tel.: +7 (921) 658-72-56. E-mail: vlasaluk@yandex.ru. ORCID: 0000-0003-1851-0941. eLibrary SPIN: 4531-6011
Yuri Sh. Halimov, MD, professor, head of the Department and clinic of military field therapy, S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia. Address: 194044, Saint Petersburg, 17 Botkinskaya Str. E-mail: yushkha@gmail.com. ORCID: 0000-0002-7755-7275. eLibrary SPIN: 7315-6746
Dmitry V. Cherkashin, MD, professor, head of the Department and clinic of naval therapy, S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia. Address: 198013, Saint Petersburg, 47 Zagorodny Avenue. E-mail: dm-cherk@yandex.ru. ORCID: 0000-0003-1363-6860. eLibrary SPIN: 621-881
Dmitry V. Kadin, PhD, senior lecturer of of the 1st Department and clinic (advanced therapy for doctors) named after academician N.S. Molchanov, S.M. Kirov Military Medical Academy of the Ministry of Defense of Russia. Address: 194044, Saint Petersburg, 6Zh Akademika Lebedeva Str. E-mail: dkadin@yandex.ru. ORCID: 0000-0003-1228-1914. eLibrary SPIN: 9703-5576


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