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Calcium-dependent insulin resistance in hepatocytes: mathematical modelстатья Исследовательская статья Электронная публикация
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 7 июля 2021 г.
- Авторы: Dokukina Irina V., Yamashev Mikhail V., Samarina Ekaterina A., Tilinova Oksana M., Grachev Eugene A.
- Журнал: Journal of Theoretical Biology
- Номер: 522
- Год издания: 2021
- Издательство: Academic Press
- Местоположение издательства: United States
- Первая страница: 110684
- DOI: 10.1016/j.jtbi.2021.110684
- Аннотация: Hepatocyte insulin resistance is one of the early factors of developing type II diabetes. If insulin resistance is treated early, type II diabetes could be prevented. In recent years, scientists have been conducting extensive research on the underlying issues on a cellular and molecular level. It was found that the modulation of IP3-receptors, the mitochondrial ability to form the mitochondria-associated membranes (MAMs) and the endoplasmic reticulum stress during Ca2+ signaling play a key role in hepatocyte being able to maintain euglycemia and provide metabolic flexibility. However, researchers cannot agree on what factor is the key one in resulting in insulin resistance. In this work, we propose a mathematical model of Ca2+ signaling. We included in the model all the major contributors of a proper Ca2+ signaling during both the fasting and the postprandial state. Our modeling results are in good agreement with available experimental data. The analysis of modeling results suggests that MAMs dysfunction alone cannot result in abnormal Ca2+ signaling and the wrong modulation of IP3-receptors is a more definite reason. However, both the MAMs dysfunction and the IP3 signaling dysregulation combined can lead to a robust Ca2+ signal and improper glucose release. In addition, our model results suggest a strong dependence of Ca2+ oscillations pattern on morphological characteristics of the ER and the mitochondria.
- Добавил в систему: Ямашев Михаил Владимирович