INS and diabetes mellitus: Generally, IR refers to the inability of insulin-target organs/tissues (e.g., skeletal muscle, adipose tissue, and liver) to produce a normal coordinated glucose-lowering response due to reduced responsiveness and sensitivity to insulin under the influence of a variety of factors, including inhibition of endogenous glucose production, inhibition of lipolysis, cellular uptake of available plasma glucose, and glycogen synthesis, resulting in the onset and worsening of glucose tolerance abnormalities and diabetes mellitus (Petersen and Shulman, 2018).