Trends in insulin resistance: insights into mechanisms and therapeutic strategy

Abstract

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into a medically manageable chronic condition. Insulin is a key peptide hormone and mediates the systemic glucose metabolism in different tissues. Insulin resistance (IR) is a disordered biological response for insulin stimulation through the disruption of different molecular pathways in target tissues. Acquired conditions and genetic factors have been implicated in IR. Recent genetic and biochemical studies suggest that the dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids and toxic lipid metabolites promote IR in other tissues. IR is associated with several groups of abnormal syndromes that include obesity, diabetes, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), and other abnormalities. Although no medication is specifically approved to treat IR, we summarized the lifestyle changes and pharmacological medications that have been used as efficient intervention to improve insulin sensitivity. Ultimately, the systematic discussion of complex mechanism will help to identify potential new targets and treat the closely associated metabolic syndrome of IR.

Fig. 1

A timeline of key discoveries in our understanding of insulin and insulin resistance

Fig. 2

The insulin signaling pathway including proximal and distal segments

Fig. 3

An integrated physiological signaling on different target tissues insulin resistance

Fig. 4

Insulin resistance related diseases in human

Fig. 5

Ex vivo diagnosis methods for insulin resistance

Fig. 6

Therapeutic strategy of insulin resistance