Regulation of insulin resistance and glucose metabolism by interaction of PIM kinases and insulin receptor substrates

Insulin resistance is caused by various environmental and genetic factors leading to a number of serious health issues. Due to its multifactorial origin, molecular characterization may provide better tools for its effective treatment. On molecular level, dysregulation of signaling pathway by insulin receptor substrates (IRSs) is one of the most common reasons of this disease. IRSs are regulated by >50 serine/threonine kinases, which may have positive or negative effects on insulin sensitivity. Among these serine/threonine kinases, PIM kinases have garnered much attention as they not only affect insulin sensitivity by phosphorylating IRSs directly and/or indirectly but also alter the activities of their downstream molecules like PI3K, AKT, and mTOR. In this review, interactions of PIM kinases with IRSs and their downstream proteins and their action mechanism in the regulation of insulin resistance are elaborated. Furthermore, this review offers fundamental understandings of the role of PIM kinases in this signaling pathway.