Saturated fatty acid induces insulin resistance partially through nucleotide-binding oligomerization domain 1 signaling pathway in adipocytes / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes.</p><p><b>METHODS</b>Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed.</p><p><b>RESULTS</b>Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.</p><p><b>CONCLUSION</b>NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.</p>

Role of sclerostin in the bone loss of postmenopausal chinese women with type 2 diabetes / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes mellitus.</p><p><b>METHODS</b>The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion. The serum sclerostin level and bone mineral density of the anterior-posterior lumbar spine (L1-L4), femoral neck, and total hip were determined by using a quantitative sandwich ELISA kit and dual X-ray absorptiometry, respectively. Meanwhile, the clinical and laboratory indexes of bone mineral metabolism were analyzed. Associations between serum sclerostin level and bone mineral density as well as bone turnover markers were evaluated by linear regression analysis.</p><p><b>RESULTS</b>Finally, 265 postmenopausal women with type 2 diabetes and 225 non-diabetic women were recruited in the diabetic group and control group, respectively. Serum sclerostin level of the diabetic group was significantly higher than that of the control group (48.2±19.4 vs. 37.2±18.6 pmol/L, P<0.001) and was increased with age in both groups (diabetic group, r=0.374, P<0.001; control group, r=0.312, P<0.001). In type 2 diabetes patients, serum sclerostin concentration was positively correlated with hemoglobin A1c level (r=0.237; P=0.021). Biochemical bone turnover markers, intact parathyroid hormone and bone-specific alkaline phosphatase, were negatively associated with serum sclerostin level (r=-0.138, P=0.078 and r=-0.265, P<0.001). Conversely, the positive correlation between sclerostin and C-terminal cross-linking telopeptide of type I collagen was found in diabetic patients (r=0.354, P<0.001). Serum sclerostin levels of the diabetic group were positively correlated with bone mineral density of the lumbar spine, femoral neck, and total hip (r=0.324, 0.367, and 0.416, respectively; all P<0.001).</p><p><b>CONCLUSIONS</b>Sclerostin might participate in the pathogenesis of bone loss of type 2 diabetes. The high sclerostin level might serve as a marker of increased osteocyte activity in postmenopausal patients with type 2 diabetes mellitus.</p>