Strenuous exercise induces oxidative stress and modification of intracellular proteins. Exercise training, however, upregulates endogenous antioxidant defenses and heat shock protein (HSP) expression. In diabetes, perturbations in the endogenous antioxidant and HSP protection have been reported. The aim of this study was to examine the effect of 8 wk of endurance training on HSP expression and oxidative stress markers in the skeletal muscle, heart, and liver of streptozotocin-induced diabetic (SID) and nondiabetic control rats. Induction of diabetes decreased HSP72 expression in heart, liver, and vastus lateralis muscles. SID increased heme oxygenase-1, an oxidative stress-inducible HSP, in liver, red gastrocnemius muscle, and vastus lateralis muscle and glucose-regulated protein 75 in liver. SID increased HSP90 levels in the heart, but levels decreased in the liver. Diabetes induced oxidative stress marker protein carbonyl levels and tissue inflammation. Although endurance training increased the expression of HSP72 in all of the tissues examined, this induction was less pronounced in diabetic rats than in nondiabetic controls. Furthermore, endurance training induced the activation and expression of transcriptional regulator heat shock factor-1 only in nondiabetic control animals. In summary, diabetes may increase susceptibility to oxidative damage and impair HSP protection, but endurance training may offset some of the adverse effects of diabetes by upregulating tissue HSP expression. Our results suggest that diabetes impairs HSP protection, possibly via transcriptionally mediated mechanisms.
diabetes is associated with impairment of endogenous tissue defense mechanisms and vulnerability of tissues to various types of stress. A major component of the endogenous defense is the heat shock protein (HSP) family, which may protect against tissue damage by facilitating the refolding of denatured proteins and maintenance of structural integrity and by acting as molecular chaperones (3). A substantial role for HSPs in diabetes and oxidative stress has emerged (15, 23, 39). It has recently been observed that skeletal muscle glucose-regulated protein (GRP) 78 and HSP90 are elevated in Type 2 diabetes mellitus (15). In contrast, streptozotocin-induced diabetes (SID) was associated with impaired HSP72 synthesis in rats (40).
Uncontrolled oxidative stress, a state in which the increased production of reactive oxygen species overwhelms endogenous antioxidant protection (17, 36), may result in damage of lipids, proteins, and genome (36). However, at lower concentrations, reactive oxygen species also serve as messenger molecules and regulate cellular adaptations. There is a general consensus that oxidative stress may have an important role in the pathophysiology of diabetes and its complications (1, 7, 9, 21). Thus the management of oxidative stress represents a key therapeutic approach to treat diabetes and its complications (1, 24, 36). The cellular redox state is known to modulate the expression of stress proteins (31).
Habitual physical exercise is a powerful tool in preventive medicine, especially for the diabetic patient. Despite possible risks of acute exercise in relation to oxidative stress in diabetic patients (1, 24), our group has previously observed that regular moderate exercise and fitness may protect diabetic men against oxidative stress (24).
It has been well demonstrated that HSP has a major role in tissue protection and repair against a number of insults and pathological conditions (33,39). Endurance training upregulates HSP expression (14, 28, 32, 33) and may provide an extra protection against oxidative stress (32, 37). The information regarding the protective effect of HSPs in tissue protection in diabetes is, however, limited. Exercise training serves as an excellent physiological model for studying mechanisms of HSP induction and enhancing tissue protection. The effect of chronic exercise on HSP expression in experimental diabetes has not been previously examined. In the present study, we tested the hypothesis that endurance training enhances tissue protection and decreases oxidative stress and tissue damage in diabetic animals through the induction of heat shock responses.