Adiponectin exerts a potent anti-arthritic effect and insulin resistance in collagen-induced arthritic rats.

AIM: Previous research has shown that adiponectin (AD) induces severe insulin resistance (IR) and exhibits pro-inflammatory effect, so it could serve as a useful risk biomarker in rheumatoid arthritis (RA). The present study aims to evaluate the effect of AD on IR and anti-arthritis in collagen-induced arthritic (CIA) rats. METHOD: After immunization with bovine type II collagen (CII), Wistar rats were administered with AD (60 µg/kg/day) or saline into the ankle joint cavity of the left hind leg for 15 days. The severity of arthritis was clinically and histologically assessed. Arthritis score was recorded every other day for each paw. Paw volume was measured on alternate days to monitor the progression of the disease in the arthritic control group. Tumor necrosis factor (TNF)-α, interleukin (IL)-1, AD, insulin and fasting glucose were measured in sera. Histopathology of joint synovial tissues was also examined. RESULTS: Treatment with AD resulted in significantly delayed onset of arthritis as well as decreased clinical arthritis and histopathological severity scores. AD reduced both serum fasting glucose, TNF-α, IL-1 and IR. Histological analysis confirmed treatment with AD suppressed joint synovial inflammation and immunohistochemical expression of TNF-α compared to the CIA group. Surprisingly, adiponectin levels measured by enzyme-linked immunosorbent assay in serum were significantly increased in CIA rats compared to the normal group. CONCLUSIONS: Adiponectin might display anti-inflammatory effects. These results suggest that AD may be a potential immunosuppressant for the treatment of RA linked to metabolic disease.

Investigation of PI3K/PKB/mTOR/S6K1 signaling pathway in relationship of type 2 diabetes and Alzheimer's disease.

The aim of this study was to investigate the roles of PI3K/PKB/mTOR/S6K1 signaling pathway in the risk-increasing mechanisms of type 2 diabetes mellitus (T2DM) towards the Alzheimer's disease (AD). Based on the high-sugar high-fat diet, the single intraperitoneal injection of streptozotocin was performed to induce the T2DM rat model; the immunohistochemistry and RT-PCR technique were then performed to detect the expression levels of mTOR, PI3K, PKB, S6K1 and phosphorylated Tau protein in the hippocampal tissues of each group. The related metabolic indicators of the T2DM group and the T2DM + AD group were significantly higher than the normal control group and the AD group (P<0.01); the Morris water maze test of the AD group and the learning and memory of the T2DM + AD group were than significantly decreased than the T2DM group (P<0.01); the T2DM + AD group exhibited significantly increased expression levels of mTOR, S6K1 and Tau protein in the hippocampal tissues than the AD group and the T2DM group (P<0.05), and while the expression levels of PI3K and PKB were decreased (P<0.05). Among the possible mechanisms through which T2DM increased the risk of AD, the dystransduction of insulin signaling pathway (PI3K/PKB/mTOR/S6K1) was the important cause of hyperphosphorylation of Tau protein, thus it prompted the AD occurrence.