This study aimed to establish a high-fat diet (HFD)-fed obese mouse model and a cell culture model of insulin resistance (IR) in mature 3T3-L1 adipocytes. A dual-luciferase reporter assay (DLRA) was confirmed interaction between miR-27a and the 3′-untranslated region (UTR) of Peroxisome proliferator-activated receptor (PPAR)-γ. The inhibition of PPAR-γ expression by microRNA (miR)-27a in IR cells at both the protein and mRNA levels was confirmed by a mechanistic investigation. Moreover, the 3′-UTR of PPAR-γ was found to be a direct target of miR-27a, based on the DLRA. Furthermore, antagomiR-27a upregulated the activation of PI3K/Akt signaling and glucose transporter type 4 (GLUT4) expression at the protein and mRNA levels. Additionally, the PPAR inhibitor T0070907 repressed the insulin sensitivity upregulated by antagomiR-27a, which was accompanied by the inhibition of PPAR-γ expression and increased levels of AKT phosphorylation and GLUT4. The PI3K inhibitor wortmannin reduced miR-27a-induced increases in AKT phosphorylation, glucose uptake, and GLUT4. miR-27a is considered to be involved in the PPAR-γ-PI3K/AKT-GLUT4 signaling axis, thus leading to increased glucose uptake and decreased IR in HFD-fed mice and 3T3-L1 adipocytes. Therefore, miR-27a is a novel target for the treatment of IR in obesity and diabetes.

Aims/IntroductionPancreatic‐derived factor (PANDER) is an important factor involved in obesity, glucose intolerance and abnormal lipid metabolism in animals. Nevertheless, the relationship between PANDER and metabolic syndrome (MetS) in humans has not yet been reported.Materials and MethodsTo determinate the relationship between PANDER and MetS components, 212 individuals aged between 40 and 65 years were recruited. Fasting plasma PANDER and other variables were measured. Correlations of plasma PANDER and other variables were carried out. Plasma PANDER level was compared in participants with no metabolic components and those with any metabolic components, as well as in normal glucose tolerance, impaired glucose tolerance and diabetes mellitus participants.ResultsIn all the participants, there were 65 participants in the no metabolic components group and 147 participants in the any metabolic components group. Plasma PANDER level was increased with the number of MetS components (P < 0.05) and correlated with metabolic score (r = 0. 529, P < 0.001). In addition, plasma PANDER significantly correlated with fasting plasma glucose (r = 0.187, P = 0.046), 2‐h plasma glucose (r = 0.195, P = 0.035), homeostasis model assessment of β‐cell function (r = −0.191, P = 0.039), triglyceride (r = 0.305, P = 0.001) and high‐density lipoprotein cholesterol (r = −0.333, P < 0.001). Using multivariable logistic regression analysis, circulating PANDER was associated with an increased risk ratio of impaired glucose tolerance or diabetes mellitus (odds ratio 2.22, 95% confidence interval 1.15–4.42, P = 0.018) after adjustment of the other possible confounders.ConclusionsCirculating level of PANDER in relation to the accumulation in MetS suggested that persons with elevated levels of PANDER were associated with an increased risk of metabolic syndrome.

Background: Brain-derived neurotrophic factor (BDNF) is involved in obesity, type 2 diabetes mellitus (T2DM), and cognitive dysfunction. The present study sought to assess the role of serum levels of BDNF in the pathophysiological process of mild cognitive impairment (MCI), a preclinical phase of dementia in 715 Chinese patients with T2DM. Methods: Cross-sectional data were obtained from 715 patients with T2DM recruited from a Chinese diabetes center. Serum levels of BDNF were measured with sandwich enzyme-linked immunosorbent assay. The influence of BDNF on MCI was examined using univariate and multivariate binary logistic regression analyses. Results: In univariate and multivariate logistic regression analyses, for each one-unit increase of BDNF, the unadjusted and adjusted risk of MCI decreased by 9% (OR 0.91; 95% CI 0.88–0.93, p < 0.001) and 6% (0.94; 0.87–0.98, p < 0.001) respectively. In multivariate models comparing the first (Q1), second and third quartiles against the fourth quartile of BDNF, BDNF in Q1 and Q2 were associated with MCI, and increased risk of MCI by 275% (OR 3.75; 95% CI 2.38–6.03) and 155% (2.55; 1.32–4.02). These results suggested that for each 1 ng/mL increase of serum level of BDNF, the association became stronger among obese diabetic patients (OR 0.91, 95% CI 0.85–0.96; p < 0.001) versus nonobese diabetic patients (OR 0.95, 95% CI 0.86–0.98; p = 0.001). Conclusion: The present data demonstrated that reduced serum levels of BDNF were associated with increased risk of MCI and might be useful for identifying diabetic patients at risk of dementia for early prevention strategies.

Aims/IntroductionElevated 1-h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut-off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long-term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis.Materials and MethodsA total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, were investigated. Follow-up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis.ResultsThe areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut-off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG ≥8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223–45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima-media thickness in the subjects with 1hPG ≥8.85 mmol/L tended to be higher compared with those <8.85 mmol/L.Conclusions1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut-off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG ≥8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis.

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