The heat shock response: its role in pathogenesis of type 2 diabetes and its complications, and implications for therapeutic intervention.

The heat shock response (HSR) is an evolutionarily conserved mechanism that cells and organisms utilize to protect themselves from the damaging effects of stress. Induction of HSR involves a complex multi-step process in which heat shock factor-1 (HSF-1), the key modulator of HSR, is activated, leading to the induction of a variety of heat shock genes. There is evidence that the HSR is defective in diabetes, which makes the tissues vulnerable to stress-induced pathological changes. Consistent with this observation, induction of HSR by either non-pharmacological methods such as hyperthermia or by pharmacological inducers has beneficial effects in managing insulin resistance and hyperglycemia, as well as secondary complications of diabetes, such as cardiovascular disease, nephropathy, neuropathy, and retinopathy as well as wound healing. This review summarizes what is currently known about the role of the HSR in diabetes and therapeutic implications of enhancing HSR in the management of diabetes and its associated complications, focusing on small molecule mediated therapeutics.