JAK inhibitors: a new choice for diabetes mellitus?

Abstract

Altered tyrosine kinase signaling is associated with a variety of diseases. Tyrosine kinases can be classified into two groups: receptor type and nonreceptor type. Nonreceptor-type tyrosine kinases are subdivided into Janus kinases (JAKs), focal adhesion kinases (FAKs) and tec protein tyrosine kinases (TECs). The beneficial effects of receptor-type tyrosine kinase inhibitors (TKIs) for the treatment of diabetes mellitus (DM) and the mechanisms involved have been previously described. Recently, several clinical cases involving the reversal of type 1 diabetes mellitus (T1DM) during treatment with JAK inhibitors have been reported, and clinical studies have described the improvement of type 2 diabetes mellitus (T2DM) during treatment with JAK inhibitors. In vivo and in vitro experimental studies have elucidated some of the mechanisms behind this effect, which seem to be based mainly on the reduction in β-cell disruption and the improvement of insulin resistance. In this review, we briefly describe the beneficial effects of JAK inhibitors among nonreceptor tyrosine kinase inhibitors for the treatment of DM and attempt to analyze the mechanisms involved.