Targeting endoplasmic reticulum stress in insulin resistance

• ER stress is implicated in the development of IR and progression to T2DM.
• Unresolved ER stress has been linked to inflammation, lipid synthesis, insulin biosynthesis and β cell apoptosis.
• Understanding the mechanisms that link ER stress and IR may provide new pharmacological targets.
• Some drugs currently used for the treatment of T2DM modulate ER stress.

The endoplasmic reticulum (ER) is involved in the development of insulin resistance and progression to type 2 diabetes mellitus (T2DM). Disruption of ER homeostasis leads to ER stress, which activates the unfolded protein response (UPR). This response is linked to different processes involved in the development of insulin resistance (IR) and T2DM, including inflammation, lipid accumulation, insulin biosynthesis, and β-cell apoptosis. Understanding the mechanisms by which disruption of ER homeostasis leads to IR and its progression to T2DM may offer new pharmacological targets for the treatment and prevention of these diseases. Here, we examine ER stress, the UPR, and downstream pathways in insulin sensitive tissues, and in IR, and offer insights towards therapeutic strategies.