Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF–α

Abstract

The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL-6) but not interleukin-10 (IL-10) or tumour necrosis factor-α (TNF-α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.

Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis

“…Recent studies have indicated that HSP70 status is intimately correlated with glycemic control and vice versa [21]. In other words, alterations in blood glucose may also interfere in HSP70 expression and its export toward the extracellular space.…”

The effect of ladder-climbing exercise on atrophy/hypertrophy-related myokine expression in middle-aged male Wistar rats

“…Thus, high levels of TNF-a and NFjB inhibited muscle hypertrophy, even though IL-6 levels were significantly increased. Ludwig et al [24] found that IL-6 increased through exercise could inhibit NFjB expression by activating HSP70, which can prevent muscle mass loss with aging. In trained young rats, IL-6 increased in response to a bout of downhill running, while TNF-a was unchanged in both sedentary and trained rats.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Within the HSP70 family, the constitutive heat shock cognate, HSC70 (or HSP73, encoded by the HSPA8 gene in humans), and its inducible form (HSP72, encoded by HSPA1A) have received more attention for their ubiquity and high level of expression. Although iHSP70 had been serendipitously discovered in heat-shocked Drosophila busckii cells by Prof. Ferruccio Ritossa in 1962 [65], HSP70 expression is associated with a variety of homeostatically stressful situations, not only heat [66]. It is noteworthy that the inducible expression of HSP72 is impressively and highly conserved in nature from bacteria to humans: in order to manage on chaperone and cytoprotective intracellular functions, at least 13 genes were identified in humans that are responsible for HSP70 family coding [35,38].…”