Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics

Abstract

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment

“…In our present study, our two mutually reinforcing hypotheses were made possible by the fact that we isolated proteins not from separated retina but from whole eyeball samples, as seen in other studies (Jiang et al, 2010;Wang et al, 2010;Varga et al, 2017;Wachal et al, 2020). On the one hand, whole eyeball contains blood vessels as well-a reasonable and main location of eHSP72 (Mahmoud et al, 2018), as blood is also extracellular-and on the other hand, increased vascular permeability, characteristic to diabetic retinopathy, further elevates the interstitial appearance of eHSP in whole eye homogenate, contributing to the high levels of total HSP70 level in untreated ZDF group in our experiment. Moreover, vascular permeability is also a consequence of NFkBactivation due to hyperglycaemia and inflammation (Romeo et al, 2002).…”

Circulating Hsp90 Isoform Levels in Overweight and Obese Children and the Relation to Nonalcoholic Fatty Liver Disease: Results from a Cross-Sectional Study

“…Another possible explanation might be the gradual development of insulin resistance and some of the overweight and obese children in the study had not yet developed insulin resistance. Nevertheless, some reports on adults did not find any difference between Hsp90 levels in type 2 diabetes and controls [18]. Future studies on insulin-resistant adult cohorts that will specifically measure Hsp90 β levels instead of circulating Hsp90 will further answer these questions and clarify the role of Hsp90 β involvement in insulin resistance.…”

Plasma heat shock protein response to euglycemia in type 2 diabetes

“…The data reported here is in accord with other reports that HSP70 and 90 did not differ significantly from the controls though; conversely, HSP70 has been reported to be elevated in T2D though HSP90 did not differ. 43 The level of HSP70-1A, a HSP70 family member, was lower in T2D than in controls, though not significantly so, in accord with those reporting lower HSP70 levels in diabetes, 44 and with the return to euglycemia the levels decreased further. HSP90 and HSP70 expression levels have been linked with T2D; 43 45 HSP70 levels have been reported to be lower in T2D, with a euglycemic clamp raising HSP70 expression while not influencing HSP90, 45 suggesting that increased glucose levels may increase HSPs that are reversed when the glucose falls to normal.…”