No abstract

ABSTRACT. Insulin resistance is a key feature of obesity and type 2 diabetes mellitus (T2DM). Interaction of insulin with the insulin receptor (IR) leads to both its auto-phosphorylation and phosphorylation of tyrosine residues on the IR substrate (IRS) proteins, initiating the activation of intracellular signaling cascades. The metabolic effects of IRS are known to be mediated through pathways involving phosphatidyl-J. Wang et al. 8820©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 8819-8828 (2015) inositol 3-kinase (PI-3K), which result in the activation of Akt signaling. The C-terminal region of the IR ectodomain is required to facilitate the conformational changes that are required for high-affinity binding to insulin. Furthermore, the CH2 and CH3 domains in the Fc fragments of immunoglobulins are responsible for their binding to the Fc receptor, which triggers transcytosis. In this study, we created a fusion peptide of the C-terminal end of the human IR ectodomain with the IgG4 Fc fragment, including an intervening polyG fragment to ensure enough space for insulin binding. We named this new peptide "Yiminsu", meaning an insulin sensitizer. The results of our analyses show that Yiminsu significantly facilitates insulin signaling via the activation of Akt in hepatocytes in a dose-and time-dependent manner. Further studies are required to determine whether Yiminsu can act as an insulin sensitizer.

We studied the lung-protective effect and mechanisms of the anti-inflammatory and antioxidant effects of ultra-short-wave diathermy (USWD) in a rat model of LPS-induced acute lung injury. Histological examination of the lung tissues was performed and the levels of oxidative stress-related factors and inflammatory cytokines were measured. It was shown that the lung injury score, the lung wet-to-dry weight ratio (W/D), oxidative stress-related factors malondialdehyde and acyl-CoA synthetase long-chain family member 4 (ACSL4), and inflammatory cytokines were increased after LPS administration, while USWD treatment reduced these parameters. In addition, superoxide dismutase and glutathione peroxidase 4 were decreased in rats with LPS-induced acute lung injury, while USWD therapy up-regulated the expression of these enzymes. Thus, USWD could antagonize lung injury by inhibiting oxidative stress and inflammatory response in rats with acute lung injury. USWD can be a promising adjunctive treatment to counter oxidative stress and inflammation and a potential therapeutic candidate for the treatment of patients with this pathology.