Banruo Sun

MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4

Abstract Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients’ plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3′UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.

The DPP-4 inhibitor MK0626 and exercise protect islet function in early pre-diabetic kkay mice

Dipeptidyl peptidase-4 (DPP-4) inhibitor and exercise have proven to be effective treatments for diabetes. However, the effects of these interventions in compensatory hyperinsulinemia prediabetic period are unknown. The purpose of this study was to determine if these interventions have protective effects on β-cell function and preventive effects on the onset of diabetes in prediabetic kkay mice. After 2 weeks of high-fat diet feeding, we treated 7-week-old mice with a normal diet, high-fat diet, exercise training, or the DPP-4 inhibitor for 8 weeks. C57BL/6J mice served as a normal control. Kkay mice without intervention developed diabetes at week 15, but no diabetic mice were observed in the DPP-4I or exercise groups as well as the normal control group. The DPP-4I and exercise groups showed improved body weight, blood glucose level, glucose tolerance, insulin sensitivity, islet area, and islet morphology. In addition, the proportion of Ki67-positive β-cells in the treatment groups was obviously higher than that in the untreated groups. MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) expression in the treated groups increased markedly. However PDX-1 (pancreatic and duodenal homeobox-1) expression did not differ significantly among the groups. The results show that exercise and DPP-4I treatment conducted during the hyperinsulinemic prediabetic stage contribute to the maintenance of β-cell function and morphology, enhance β-cell proliferation, extend the compensatory insulin hypersecretion period, and delay disease onset. The expression of PDX-1 was not altered significantly during the early stages of diabetes. However, the reduced expression of the insulin transcription factor MafA may play an important role in the development of prediabetes.

Retraction Note to: Adipose stromal-vascular fraction-derived paracrine factors regulate adipogenesis

Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to metabolic disease. Therefore, the adipogenic potential of different fat depots was investigated and found to be higher in subcutaneous compared with visceral stromal–vascular fraction (SVF), which contains adipocyte precursor cells. This increased differentiation capacity was not due to elevated numbers of Lin−Sca1+CD29+CD34+Pref1+ precursor cells, as the number of preadipocytes was higher in visceral than in subcutaneous SVF. The secreted heat-sensitive factors from the SVF inhibited adipocyte differentiation more in visceral than in subcutaneous SVF. In order to explore secreted proteins that potentially inhibit differentiation, the secretome of murine SVF was analyzed by mass spectrometry, which resulted in the identification of 113 secreted proteins with an overlap of 42 % between subcutaneous and visceral SVF. Comparison of the mRNA expression in SVF from both depots revealed 16 transcripts that were significantly expressed more in visceral than in subcutaneous SVF. A functional differentiation screen identified seven potential inhibitory candidates: biglycan, decorin, bone morphogenic protein 1, epidermal growth factor-containing fibulin-like extracellular matrix protein 2, elastin microfibril interfacer 1, matrix gla protein, and Sparc-like 1. For further verification, murine recombinant decorin or Sparc-like 1 was added to the media during the differentiation process leading to a dose-dependent decrease in adipogenesis. Further analysis will be necessary to assess the impact of the other candidates on adipocyte differentiation.

Association between sex hormone levels and abnormal metabolism in a population of elderly Chinese men.

Abstract Objective: Low testosterone levels may be a signal of poor health. This study aimed to investigate the effects of age and abnormal metabolism on sex hormones in Chinese male. Methods: Three hundred and thirty-seven elder men were enrolled into this single-center, cross-sectional study, and their sex hormone levels and metabolic parameters were assessed. Results: Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone-binding globulin (SHBG) concentrations increased with age, while free testosterone index (FTI), testosterone secretion index (TSI), estradiol (E2)/SHBG and progestin (PROG) decreased. Abnormal metabolisms were related to androgen indices (TT, FT, BT, FTI, TSI, T/E2), SHBG and E2/SHBG even after adjusting by age and macrovascular disease. Obesity and overweight, hyperglycemia and dyslipidemia were the most important abnormal metabolism that related to decreased androgen indices. Including SHBG in the stepwise regression increased the explanation effect of TT and BT by 32.7% and 28.5%, respectively, and all metabolic indices were excluded. Abnormal metabolism indies (BMI and PBG) were correlated to the decrease in SHBG levels, while age and LH was positively correlated to SHBG levels. Conclusions: Age and abnormal metabolism were independently important factors associated with the sex hormone levels in elderly Chinese men, which were all mediated by SHBG.

Effects of body mass index and weight change on mortality in older men with impaired glucose regulation

Objectives: To assess the effect of baseline body mass index (BMI) status and weight change on mortality in older men with impaired glucose regulation (IGR). Methods: Eight hundred eighty‐five men with IGR aged 60 to 90 were included. Baseline and endpoint weight were measured. All‐cause and cardiovascular mortality were observed during a median follow‐up period of 10 years. Multivariate Cox regressions were used to estimate associations between BMI, weight change and mortality. Results: Relative to normal weight, overweight was associated with lower all‐cause mortality (hazard ratios, HRs [95% confidence interval, 95% CI]: 0.57 [0.41, 0.78]) and cardiovascular mortality (0.52 [0.29, 0.93]), whereas obesity did not significantly decrease or increase the mortality risk. Furthermore, compared to weight stability, all types of weight change led to increased mortality risk, except small weight gain. Specifically, after adjustment for covariates and the initial weight, the HRs (95% CI) of large weight loss were 1.64 (1.15, 2.34) for all‐cause mortality and 1.85 (1.10, 3.14) for cardiovascular mortality, and the HRs (95% CI) of large weight gain were 1.55 (1.01, 2.40) for all‐cause mortality and 2.11 (1.04, 4.30) for cardiovascular mortality. Similar associations were observed when weight change was redefined in sensitivity analyses. Conclusions: Both BMI at baseline and weight change have independent U‐shaped associations with all‐cause and cardiovascular mortality among older men with IGR. The present study suggests that older men with IGR may ensure their best survival by being overweight at baseline or by maintaining their weight regardless of their baseline weight status. HighlightsEffects of obesity and weight loss on death remain controversial in the elderly.Body mass index had a U‐shaped association with mortality in older men with IGR.Weight change had a U‐shaped association with mortality in older men with IGR.Older men with IGR may benefit from being overweight or maintaining their weight.

Metabolic diseases and sex hormone levels affect differently in the development of cardiovascular and cerebrovascular diseases in elderly males.

Abstract Objective: This single-centre cross-sectional study aimed to investigate the metabolic and gonadal risk factors of vascular diseases in elderly males. Methods: After screening, 337 subjects aged 60–90 were found to be qualified. Odds ratios (ORs) in cross-table analyses and exp(B) in logistic regression analyses were used to evaluate the vascular risk of dependent factors. R2 of logistic regression equation was used to estimate the goodness-of-fit of vascular diseases logistic regression models. Results: Hypertension increased the risk of cardiovascular disease (CAVD) in elderly men approximately 3-fold. The number of metabolic diseases also correlated with incremental risks of CAVD; presence of one abnormality approximately increases the risk approximately 62%. Cerebrovascular disease (CEVD) development was closely associated with both metabolic syndrome and sex hormone levels; their explanation effects of single action and combined action were 13.2%, 12.55% and 28.5%. C-peptide might be the underlying mechanism of the metabolic syndrome’s effect on CEVD. C-peptide = 2.43 U/L and FE2 = 0.66 were the tangent points in receiver operating characteristic (ROC) analyses. Conclusions: Metabolic diseases and sex hormones play different roles in the development of CAVD and CEVD, the methods for vascular protection in elderly men should be promoted differently according to the their risks of CAVD and CEVD.

Testosterone level in aging male with different glucose tolerance state and its association with osteocalcin

Abstract Objective: To investigate the relationship of testosterone and different glucose tolerance state, and its association with osteocalcin. Methods: A cross-sectional study was conducted of 1176 males aged 60–97 years who were arranged for an annual regular checkup from March to May 2012 in Chinese PLA general hospital in Beijing. Results: Individuals categorized as having prediabetes or diabetes were more likely to have lower osteocalcin, testosterone, and SHBG levels compared to those with normal glucose tolerance (p < .05 in males). In aging males, after adjusting for age, the negative association between osteocalcin and BMI, waist circumference, FPG, 2hPBG, or TG were significant. And serum TT was negatively associated with BMI, waist circumference, FPG, 2hPBG, or TG independent of age, ALP, Ca, P, VitD, and PTH. Conclusions: It showed that serum osteocalcin and TT were closely related with BMI, blood glucose, and TG, which supported the hypothesis that regulation of bone remodeling, energy metabolism, and reproduction are linked.

Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

The incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.