Signaling pathways and intervention for therapy of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID-19). T2DM is characterized by insulin resistance (IR) and pancreatic beta cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and beta cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.

Automated summary

T2DM is a rapidly growing epidemic metabolic disorder associated with various comorbidities and recent data suggest a connection between T2DM and COVID-19. T2DM is characterized by insulin resistance and beta cell dysfunction, and understanding signaling pathways related to T2DM can provide potential targets for therapy. This review provides an overview of the history of T2DM and signaling pathways, discusses the role and mechanism of key signaling pathways in the development of T2DM, and summarizes current therapeutic options.