Jiao-Yue Zhang

The protective effect of resveratrol on islet insulin secretion and morphology in mice on a high-fat diet

The aim of this study was to investigate the effect of resveratrol on beta cells in male C57BL/6J mice fed a high-fat diet and the possible mechanisms. Male C57BL/6J mice were randomly divided into three groups: normal control (NC) group, high-fat diet (HF) group and high-fat diet and resveratrol treatment (HFR) group (15 in each group). HFR group was fed with high fat diet for 8 weeks and then orally administered resveratrol at 400mg/kg daily. Twenty-four weeks later, the function of insulin secretion in vivo and in vitro was improved robustly in HFR group compared with HF group. The levels of glucose and lipid metabolism, beta cell mass, lipid content, and oxidative stress were lower in HFR group than in HF group. Simultaneously, resveratrol administration promoted the expression of SIRT1 in islets, while the expression of uncoupling protein 2 (UCP2) was restrained. Resveratrol, as well, also had a beneficial effect on the ratios of expressions of Bcl-2/Bax and levels of malondialdehyde/glutathione peroxidase. Resveratrol can protect islets from abnormal insulin secretion and morphological changes induced by a high-fat diet. The effect might be partly related to activated SIRT1 signal pathway, improved oxidative stress induced damage and incidence of apoptosis.

Relationship between Serum TSH Level with Obesity and NAFLD in Euthyroid Subjects

SummaryTo explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects, 1322 subjects were subjected to a questionnaire survey and physical examination. Fasting blood samples were collected to test serum TSH, plasma glucose and lipids. Fatty liver was diagnosed by type B ultrasonography. The relationship between serum TSH level and body mass index (BMI), percentage of body fat and NAFLD was analyzed. The results showed that serum TSH level was significantly higher in females than in males at the same group, and it was significantly higher in overweight group than in control group. Levels of body weight, BMI, waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women. However, plasma lipids showed no significant differences. In males all the parameters showed no significant differences between two groups. Serum TSH was significantly correlated with body weight, BMI, waist circumference and percentage of body fat after adjustment for age in females. Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH. Serum TSH level was significantly higher in nonalcoholic fatty liver group than in normal group in females. Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD. Taken together the data suggest that serum TSH in normal range is significantly correlated with BMI and percentage of body fat in females. And the change of TSH level would not influence the prevalence of NAFLD.To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects, 1322 subjects were subjected to a questionnaire survey and physical examination. Fasting blood samples were collected to test serum TSH, plasma glucose and lipids. Fatty liver was diagnosed by type B ultrasonography. The relationship between serum TSH level and body mass index (BMI), percentage of body fat and NAFLD was analyzed. The results showed that serum TSH level was significantly higher in females than in males at the same group, and it was significantly higher in overweight group than in control group. Levels of body weight, BMI, waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women. However, plasma lipids showed no significant differences. In males all the parameters showed no significant differences between two groups. Serum TSH was significantly correlated with body weight, BMI, waist circumference and percentage of body fat after adjustment for age in females. Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH. Serum TSH level was significantly higher in nonalcoholic fatty liver group than in normal group in females. Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD. Taken together the data suggest that serum TSH in normal range is significantly correlated with BMI and percentage of body fat in females. And the change of TSH level would not influence the prevalence of NAFLD.

Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet.

Insulin therapy has been shown to contribute to extended glycemia remission in newly diagnosed patients with type 2 diabetes mellitus. This study investigated the effects of insulin treatment on pancreatic lipid content, and β-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on β-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic β-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative β-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet β-cell secreting function was assessed by the index ΔI30/ΔG30. Glucose-intolerant rats had higher pancreatic lipid content, more islet β-cell apoptosis, lower β-cell proliferation, and reduced β-cell area in pancreas when compared with controls. Insulin therapy reduced blood glucose, inhibited pancreatic lipid accumulation and islet β-cell apoptosis, and increased β-cell proliferation and β-cell area in glucose-intolerant rats. Furthermore, impaired insulin secretion and insulin production in glucose-intolerant rats were improved by insulin therapy. Insulin can preserve β-cell function by protecting islets from glucotoxicity and lipotoxicity. It can also ameliorate β-cell area by enhancing β-cell proliferation and reducing β-cell apoptosis.

Liraglutide prevents fast weight gain and β-cell dysfunction in male catch-up growth rats.

We reported recently that after a nutritional growth retardation, rats showed significant weight gain, central fat accumulation, dyslipidemia, and β-cell dysfunction during a catch-up growth (CUG) phase. Here, we investigated whether glucagon-like peptide-1 (GLP-1) ameliorated the rapid weight gain, central fat deposition, and β-cell dysfunction during the CUG in rats. Sixty-four male Sprague Dawley rats were stratified into four groups including normal control group, CUG group, catch-up growth with liraglutide treatment group, and catch-up growth with liraglutide and exendin 9–39 treatment group. Energy intake, body weight, and body length were monitored. Fat mass percentage was analyzed by dual energy X-ray absorptiometry scan. Plasma triglyceride and non-esterified fatty acid were measured. The β-cell mass was analyzed by morphometric analysis and signaling molecules were examined by Western blot and real-time PCR. Insulin secretion capability was evaluated by hyperglycemic clamp test. Liraglutide prevented weight gain and improved lipid and glucose metabolism in rats under CUG conditions, which were associated with reduced fasting insulin levels and improved glucose-stimulated insulin secretion. Improved β-cell function is found to be associated with increased β-cell replication as determined by β-cell density and insulin-Ki67 dual staining. Furthermore, liraglutide increased islet pancreatic duodenal homeobox-1 (Pdx-1) and B-cell lymphoma-2 transcript and protein expression, and reduced Procaspase-3 transcript and Caspase-3 p11 subunit protein expression, suggesting that expression of Pdx-1 and reduction of apoptosis may be the mechanisms involved. The therapeutic effects were attenuated in rats co-administered with exendin 9–39, suggesting a GLP-1 receptor-dependent mechanism. These studies revealed that incretin therapy effectively prevented fast weight gain and β-cell dysfunction in rats under conditions of nutrition restriction followed by nutrition excess, which is in part due to enhanced functional β-cell mass and insulin secretory capacity.

Increases in systemic and local stress: a probable mechanism of visceral fat accumulation and insulin resistance in adult catch-up growth rats?

Catch-up growth in adult (CUGA) is increasingly proposed as an important causative factor for the widespread insulin resistance (IR)-related diseases especially in developing countries/territories. We aimed to investigate the effects of CUGA to insulin sensitivity, lipid profile and stress in rats, as well as the probable relationship among them. Male Sprague-Dawley rats were randomly divided into six groups for two sampling points: caloric restriction group (R4) and normal chow controls for four weeks (NC4); CUGA re-fed with normal chow (RN4), CUGA re-fed with high-fat diet (RH4), normal chow controls (NC8) and high-fat diet controls (HF8) for eight weeks. Visceral fat accumulation (visceral adipose tissue [VAT] percentage), systemic (plasma corticosterone) and local (HSD11B1 mRNA expression in skeletal muscle [SkM] and VAT) stress, whole-body and peripheral insulin sensitivity were determined in this study. After four weeks of caloric restriction, R4 rats showed increases in systemic and local stress, decreases in visceral fat accumulation and no IR (whole-body or peripheral). Yet, after re-feeding, sustained systemic and local stress, remarkable visceral fat accumulation and IR (whole-body and peripheral) were found in RN4 compared with NC8, in RH4 compared with NC8 and HF8. Our findings demonstrated that CUGA rats were characterized by significant IR, visceral fat accumulation and stress. These changes were more severe in CUGA re-fed with high-fat diet. The interaction of sustained caloric restriction-induced stress and re-feeding might be of utmost importance in the etiology of visceral fat accumulation and IR in CUGA.

Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth

Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult.

Elevated circulating Neuregulin4 level in patients with diabetes

Neuregulin4 (Nrg4) is a novel adipokine expressed in adipose tissues, enriched in brown adipose tissue, and able to improve whole‐body metabolism in rodent, thus having the potential to treat obesity‐associated disorders such as diabetes. However, the association between serum Nrg4 levels and diabetes risk in human remains unclear. This study was designed to examine circulating Nrg4 levels in subjects with different glucose tolerance status.

Relocation potentiates obesity and cardiovascular risk: A case-control study on relocatees from the Three Gorges area.

Highlights •Relocatees of The Three Gorges, compared with original inhabitants, are at higher risk of general and abdominal obesity, and other metabolic disorders associated with cardiovascular risk, such as insulin resistance, dyslipidemia, and metabolic syndrome. • The process of rapid nutritional transition from under-nutrition to subsequent nutritional restoration in adulthood, which is associated with the relocation, may be one of the major factors for the metabolic disorder epidemic in Asia.

Indoor renovation and diabetes mellitus: Evidence from a cohort study: 室内装修与糖尿病:来自一项队列研究的证据

In 2015, diabetes mellitus (DM), a major global challenge, caused death every 6 s. In the same year, 12% of global health expenditure was spent on diabetes. Thus, it is important to prevent the development of diabetes. There is growing public concern regarding household or workplace renovations that cause indoor air pollution. Volatile organic compounds (VOCs), formaldehyde, ammonia, benzene, xylene, and radon are the main pollutants after indoor renovations. Diseases related to the nervous and respiratory systems, as well as certain cancers related to these pollutants have been reported. However, to the best of our knowledge, the relationship between household or workplace renovations and the risk of DM remains uncertain. Thus, the aim of the present study was to evaluate the effects of renovations on diabetes by analyzing data from a cohort in central China.

Non-high-density lipoprotein cholesterol: High-density lipoprotein cholesterol ratio is an independent risk factor for diabetes mellitus: Results from a population-based cohort study: 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值是糖尿病的独立危险因素:来自一项基于人群的队列研究的结论

Dyslipidemia predicts the development and progression of diabetes. A higher non‐high‐density lipoprotein cholesterol (HDL‐C):  HDL‐C ratio is reportedly associated with metabolic syndrome and insulin resistance, but its relationship with glycemic levels and diabetes remains unclear.