Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

Venojärvi, Mika; Korkmaz, Ayhan; Aunola, Sirkka; Hällsten, Kirsti; Virtanen, Kirsi A.; Marniemi, Jukka; Halonen, J.-P.; Hänninen, Osmo; Nuutila, Pirjo; Atalay, Mustafa

doi:10.1155/2014/386351

Cited by 16 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A marked upregulation of iHsp90 in skeletal muscles has been reported in type 2 diabetes patients (Venojarvi et al 2014). In the present study, plasma levels of eHsp90 were increased, but not to a significant level relative to healthy control subjects (Table 2).…”

Section: Discussionsupporting

confidence: 60%

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

Mahmoud

Haines

Dashti

et al. 2018

Cell Stress and Chaperones

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 60%

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

Mahmoud

Haines

Dashti

et al. 2018

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…While HSP90 has not been described in laminitic horses, the heat shock response has been found to be altered during type 2 diabetes in humans (52). For instance, HSP90 is higher in type 2 diabetic humans than in those with only impaired glucose tolerance (53), and inhibition of HSP90 appears to limit renal and vascular damage in diabetic mice (54). It is also worth noting that while laminitis is already well-associated with atherosclerotic markers, HSP90 inhibitors may reduce atherosclerosis during diabetes (55) and restore glucocorticoid sensitivity during Cushing's disease (56).…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis

et al. 2020

View full text Add to dashboard Cite

Endocrinopathic laminitis is pathologically similar to the multi-organ dysfunction and peripheral neuropathy found in human patients with metabolic syndrome. Similarly, endocrinopathic laminitis has been shown to partially result from vascular dysfunction. However, despite extensive research, the pathogenesis of this disease is not well elucidated and laminitis remains without an effective treatment. Here, we sought to identify novel proteins and pathways underlying the development of equine endocrinopathic laminitis. Healthy Standardbred horses (n = 4/group) were either given an electrolyte infusion, or a 48-h euglycemic-hyperinsulinemic clamp. Cardiac and lamellar tissues were analyzed by mass spectrometry (FDR = 0.05). All hyperinsulinemic horses developed laminitis despite being previously healthy. We identified 514 and 709 unique proteins in the cardiac and lamellar proteomes, respectively. In the lamellar tissue, we identified 14 proteins for which their abundance was significantly increased and 13 proteins which were significantly decreased in the hyperinsulinemic group as compared to controls. These results were confirmed via real-time reverse-transcriptase PCR. A STRING analysis of protein-protein interactions revealed that these increased proteins were primarily involved in coagulation and complement cascades, platelet activity, and ribosomal function, while decreased proteins were involved in focal adhesions, spliceosomes, and cell-cell matrices. Novel significant differentially expressed proteins associated with hyperinsulinemia-induced laminitis include talin−1, vinculin, cadherin-13, fibrinogen, alpha-2-macroglobulin, and heat shock protein 90. In contrast, no proteins were found to be significantly differentially expressed in the heart of hyperinsulinemic horses compared to controls. Together, these data indicate that while hyperinsulinemia induced, in part, microvascular damage, complement activation, and ribosomal dysfunction in the lamellae, a similar effect was not seen in the heart. In brief, this proteomic investigation of a unique equine model of hyperinsulinemia identified novel proteins and signaling pathways, which may lead to the discovery of molecular biomarkers and/or therapeutic targets for endocrinopathic laminitis.

show abstract

“…The up-regulation of the HSP90 in the STZ-induced pancreas [ 51 ] appears to confer inadequate protection for β-cells. In fact, increased expression of HSP90 is observed in skeletal muscle biopsies of T2DM subjects [ 52 ]. Moreover, SOD2 expression was significantly reduced in the STZ-induced pancreas.…”

Section: Discussionmentioning

confidence: 99%

Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

et al. 2015

View full text Add to dashboard Cite

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels.

show abstract

Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

Cited by 16 publications

References 38 publications

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

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

Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis

Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

Contact Info

Product

Resources

About