Loss of defense against stress: diabetes and heat shock proteins.

WE PROPOSE THAT DIABETES produces a vulnerable condition with impaired defenses against stress, resulting in widespread unprotected organ systems. More specifically, the ultimate natural history of diabetes and its complications is determined by the net effect of diabetes-induced inflammation, oxidation, and glycation, as well as an induced deficiency of heat shock factor-1 (HSF-1) that subsequently reduces the stress proteins that HSF-1 stimulates—heat shock proteins (Hsps) 60, 70, and 90. (Hsp 70 is also termed Hsp 72.) Furthermore, we speculate that reduced HSF-1 and Hsp levels are the result of an insulin resistance– diabetes-induced loss of membrane fluidity. The hypothesis is based on the following observations: (1) HSF-1 and Hsp levels are low in animal models of diabetes, in human subjects with diabetes, and in people with just insulin resistance. (2) Low Hsp levels lead to cells and tissues that are susceptible to injury with shortened viability. (3) Medications and lifestyles that raise Hsp levels improve diabetes complications and slow the progression of diabetes. WHAT ARE Hsps?