problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201561644-54problendo-7726Research ArticleОбзорыReviewsПерспективные фармакологические мишени для лечения заболеваний, сопряженных с дефектом сигнального пути рецептора инсулинаPromising pharmacological targets for the treatment of the diseases associated with the impaired insulin receptor signaling pathwayГорбуновЕвгений АлександровичGorbunovEvgeniy Aleksandrovich

старший научный сотрудник, научно-аналитический отдел

gorbunovea@materiamedica.ruБригадироваАнастасия АндреевнаBrigadirovaAnastacia Andreevna

ассистент кафедры фармакологии ГБОУ ВПО ВолгГМУ Минздрава РФ,

младший научный сотрудник лаборатории экспериментальной фармакологии ГБУ ВМНЦ

MD

a.brigadirova@gmail.comКачаеваЕвгения ВладимировнаKachaevaEvgeniya Vladimirovna

кандидат биологических наук, начальник отдела международной медицинской документации

PhD

kachaevaev@materiamedica.ruПутиловскийМихаил АлександровичPutilovskiyMikhail Aleksandrovich

кандидат медицинских наук, заместитель генерального директора, начальник отдела клинических исследований  

MD, PhD

putilovskiy@materiamedica.ruТарасовСергей АлександровичTarasovSergey Aleksandrovich

кандидат медицинских наук, начальник научно-аналитического отдела

MD, PhD

tarasovsa@materiamedica.ruООО «НПФ «МАТЕРИА МЕДИКА ХОЛДИНГ»РоссияNPF “MATERIA MEDICA HOLDING” LLCRussian FederationГБОУ ВПО «Волгоградский государственный медицинский университет» Минздрава России; ГБУ «Волгоградский медицинский научный центр»РоссияVolgograd State Medical University; Volgograd Medical Research CenterRussian Federation2015301120156164454Copyright © Горбунов Е.А., Бригадирова А.А., Качаева Е.В., Путиловский М.А., Тарасов С.А., 20152015Горбунов Е.А., Бригадирова А.А., Качаева Е.В., Путиловский М.А., Тарасов С.А.Gorbunov E.A., Brigadirova A.A., Kachaeva E.V., Putilovskiy M.A., Tarasov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/7726

Сахарный диабет (СД) занимает одно из первых мест в мире среди наиболее распространенных хронических заболеваний. При СД 2-го типа (СД2) наблюдается стойкая инсулинорезистентность, обусловленная нарушением способности гормона стимулировать захват глюкозы клетками-мишенями и снижать уровень глюкозы в крови. В основе этого лежит, вероятнее всего, нарушение передачи сигнала от рецептора инсулина (ИР) к внутриклеточным инсулинзависимым сигнальным каскадам. Оптимизация существующих и разработка ранее не задействованных подходов к терапии СД позволяет считать актуальной задачей поиск новых мишеней для создания инновационных антидиабетических соединений. Среди множества возможных мишеней особое место занимает ИР и ассоциированные с ним сигнальные пути. В обзоре уделяется внимание строению ИР и функционированию сопряженных с ним сигнальных путей. Представлены данные о новых лигандах-миметиках и сенситайзерах ИР, а также о других молекулах, способных влиять на различные компоненты сопряженных с ИР сигнальных путей, тем самым проявляющих конкретный антидиабетический эффект. Действие данных соединений направлено на коррекцию основных метаболических нарушений, приводящих к гипергликемии, и условно сводится к следующим эффектам: активации и потенцированию инсулиновой сигнализации, улучшению чувствительности периферических тканей к инсулину; восстановлению физиологических механизмов секреции инсулина; снижению повышенной продукции глюкозы печенью.

Diabetes mellitus (DM) is one of the most widespread chronic diseases in the world. In DM type 2, peripheral tissues demonstrate strong resistance to endogenous insulin (insulin resistance) which is caused by impaired ability of the hormone to stimulate glucose uptake in target cells (muscle, adipose or brain tissue, liver, etc.) and to reduce blood glucose level. Research data suggest that all mentioned reasons are most likely to be based on a disruption of signal transduction from insulin receptor (IR) into insulin-dependent intracellular signaling cascades. Contemporary DM treatment strategy is aimed at the maintenance of optimal blood glucose level by improving insulin production and increasing insulin sensitivity of tissue as well as prevention of macro- and microvascular complications and decrease of their intensity. At the same time, the search for new targets for creation of innovative anti-diabetic compounds can be considered a promising task due to the optimization of existing approaches and development of the novel ones taking into account results of the latest research into DM etiology and pathogenesis. A special position among possible targets is occupied by insulin receptor (IR) and IR-associated signaling pathways. Belonging to tyrosine kinase receptor family, IR has been actively studied during the last decades. This review considers in particular the IR structure and functioning of receptor-associated signaling pathways. The paper contains data on novel ligand-mimetics and IR sensitizers as well as other molecules, which affect different components of IR-associated signaling pathways, thus exerting significant antidiabetic effect. Action of these compounds is aimed at improvement of basic metabolic disorders resulting in hyperglycemia and is mainly carried out due to the following effects: activation and potentiation of insulin signaling, increase of insulin sensitivity of peripheral tissues; recovery of insulin secretion physiological mechanisms; reduction of glucose production in liver.

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The authors declare that there are no conflicts of interest present.