Inflammation, heat shock proteins, and type 2 diabetes

Abstract

We propose that type 2 diabetes results from a vicious cycle of metabolically induced inflammation, impaired insulin responsiveness, and subsequent loss of homeostatic signaling. A crucial and previously under-recognized event contributing to this loss of homeostasis is a reduction in heat shock proteins (HSPs, or stress proteins). The central causal pathways of this cycle are the following: (a) obesity-driven inflammation promotes insulin resistance; (b) impaired insulin signaling in turn reduces the expression of HSPs, leaving tissues vulnerable to damage and allowing the accumulation of harmful proteins aggregates; and (c) resulting damage to the pancreatic beta-cell leads to further losses in insulin signaling, while a decline in anti-inflammatory HSPs allows inflammation to expand unhindered. Obesity and sedentary lifestyle perpetuate this cycle, while dieting and exercise forestall it by raising HSPs, reducing inflammation, and improving insulin signaling. Because HSP expression carries substantial metabolic costs, it is likely that an evolutionary history of high activity levels and resource scarcity selected for more conservative HSP expression than is appropriate for our current environment of caloric abundance.

Hyperbaric oxygen therapy (HBOT) suppresses biomarkers of cell stress and kidney injury in diabetic mice

“…The anti-inflammatory action of HBOT may arise in part from its ability to increase the expression of antioxidant genes and other cellular defense genes through the induction of a noncytotoxic oxidative stimulus (Matsunami et al 2009(Matsunami et al , 2011Simsek et al 2011;Godman et al 2010a, b;He et al 2011). Expression of these genes can provide insights into the metabolic state of the tissue under different physiological conditions (Hooper and Hooper 2009;Hooper et al 2014). Evidence that HBOT can condition tissues to promote function and survival comes from the study of rat models of myocardial infarction (Han et al 2008;Sun et al 2011) and cerebral ischemia reperfusion injury (Li et al 2008(Li et al , 2009Cheng et al 2011), as well as a mouse model of repeated UV-A skin exposure (Fuller et al 2013).…”

Anemia its presence and severity in type 2 DM and its relationship with micro and macro vascular complications

“…Obesity is associated with the development of an inflammatory state especially in adipocytes and muscle cells thus leading to increase circulation of blood glucose resulting in hyperglycemic state. 19 Adipose tissue has more recently been recognized as a metabolically active organ system linking the endocrine and immune systems; furthermore it a source of variety of cytokines. 20 It was also found in our study that the systolic BP and diabetic BP in diabetic patients that were anemic was significantly higher when compared to non-anemic cases.…”

Application of High-Dimensional Statistics and Network Based Visualization Techniques on Arab Diabetes and Obesity Data

“…Recent evidence indicated that the uncontrolled inflammatory response and metabolic stress are highly integrated and they likely work in vicious cycles [9,18,19]. This represents one of the greatest challenges to identify therapeutic targets for the treatment and management of these metabolic disorders [20,21]. At the molecular level, the existence of such an environment leads to the activation of c-Jun NH2 terminal kinase (JNK) [22], and the Inflammatory B Kinase (IKK) [23].…”