Pleiotropic effects of polyphenols on glucose and lipid metabolism: Focus on clinical trials

Epidemiological evidence from observational studies suggests that dietary polyphenols (PPs) – phytochemicals found in a variety of plant-based foods – can reduce the risk of developing type 2 diabetes mellitus (T2DM). Clinical trials have also indicated that PPs may help manage the two key features of T2DM, hyperglycemia and dyslipidemia. Since the incidence of T2DM is dramatically increasing worldwide, identifying food-based approaches that can reduce the risk of developing it and help manage its main risk factors in early-stage disease has clinical and socioeconomic relevance.After a brief overview of current epidemiological data on the incidence of T2DM in individuals consuming PP-rich diets, we review the evidence from clinical trials investigating PP-enriched foods and/or PP-based nutraceutical compounds, report their main results, and highlight the knowledge gaps that should be bridged to enhance our understanding of the role of PPs in T2DM development and management.     

高密度脂蛋白亚类抗脂多糖作用的研究

目的:探讨不同的高密度脂蛋白(HDL)亚类抗脂多糖(LPS)作用。方法:转染NF-κB-luc报告质粒至HepG2细胞,分析HDL各亚类对经LPS刺激的转染细胞荧光素酶表达的影响、HDL亚类与转染细胞孵育对LPS诱导的荧光素酶表达的影响以及HDL与LPS孵育对LPS诱导的荧光素酶表达的影响;运用逆转录-多聚酶链反应(RT-PCR)技术,分析HDL亚类与LPS孵育对LPS诱导的TNF-α mRNA表达的影响。结果:大颗粒HDL2孵育的细胞荧光素酶表达显著受到抑制;HDL3孵育的细胞荧光素酶表达略有降低;preβ1-HDL孵育的细胞荧光素酶表达未见改变;LPS-HDL2复合物刺激的细胞荧光素酶表达显著受到抑制;LPS-HDL2复合物刺激的细胞TNF-α mRNA的表达也显著降低。结论:成熟的大颗粒HDL2能够显著抑制LPS诱导的荧光素酶活性以及TNF-α mRNA的表达,表明HDL2具有较强的结合和中和LPS的能力。     

血清HDL亚类分布特征及与载脂蛋白的关系

目的：分析人群中HDL各亚类的频数分布特征及探讨载脂蛋白含量与HDL亚类含量、分布变化的关系。方法:采用双向电泳-免疫印迹方法检测血清HDL亚类含量，Kolmogorov-Smirnov检验HDL亚类分布类型,直线相关及多元线性回归分析血清HDL亚类分布与载脂蛋白关系。结果:血清preβ2-HDL、HDL3a、HDL2a、HDL2b呈正态分布，preβ1-HDL、HDL3b、HDL3c呈偏态分布；女性HDL-C、apoAI、HDL2a及HDL2b的含量显著高于男性，而preβ1-HDL及HDL3c的含量则显著低于男性；相关分析发现apoAI含量与所有亚类的水平呈显著正相关（r值在0.365-0.577范围，P<0.01），apoB100、apoCII、apoCIII、apoE与Preβ1-HDL及HDL3a的水平呈显著正相关（r值在0.139-0.489范围，P<0.01），但与HDL2a、HDL2b的水平呈显著负相关（r值在-0.122~-0.386范围，P<0.01）；多元线性回归分析表明：apoAI对HDL各亚类含量变化影响最大（β值在0.385-0.601范围,P<0.01）。结论:血清preβ2-HDL、HDL3a、HDL2a、HDL2b呈正态分布，preβ1-HDL、HDL3b、HDL3c呈偏态分布。apoAI与HDL各亚类含量均呈显著正相关并且对亚类含量变化的影响最大;apoB100及apoCII、apoCIII和apoE与小颗粒的Preβ1-HDL呈显著正相关（r值在0.355-0.489范围，P<0.01），而与大颗粒的HDL2a或HDL2b呈显著负相关（r值在-0.122~-0.386范围，P<0.01）。     

Evolution of hepatocellular carcinoma associated with chronic hepatitis B virus infection in Alaskan Eskimos

Hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection in Yupik Eskimos in southwestern Alaska, detected in early stages as a result of screening, appears to be more frequently associated with variants of chronic portal inflammation in the noninvolved liver than with fully developed cirrhosis, otherwise common in HBV-associated HCC from other geographic areas. Of 38 patients diagnosed with HCC since 1969, adequate tissue was available from both the tumor and nontumorous liver in 17. Of the 17 specimens, 14 had chronic portal inflammation and three had advanced cirrhosis; 12 of the 14 were from hepatitis B surface antigen carriers. These 12 cases were studied in detail to examine the features accompanying the development of HCC unobscured by cirrhotic transformation. In the noninvolved parenchyma they included hepatocytic nodules as apparent precursors to HCC and, as markers of phenotypic alterations, dysplastic hepatocytes and hepatitis B surface antigen-laden ground-glass hepatocytes. The latter were observed in eight instances and often accumulated in nodules. Parenchyma within 1 mm of the HCC exhibited increased confluent hyperplasia and frequently conspicuous necroinflammation associated with pericellular and periductular fibrosis, which contributed, in addition to fibrous connections between displaced and heavily inflamed portal tracts, to the capsule that was forming in all cases to varying degrees in the pericarcinomatous region. The HCC was uniformly trabecular and in a few specimens, a continuous transition from hyperplasia and dysplasia near the periphery of the tumor to increasing anaplasia in the center could be made out in addition to pressure effects of the HCC. The pericarcinomatous changes, including hyperplasia progressing to neoplasia and necroinflammation, are also observed in experimental models, particularly the woodchuck HCC induced by a hepadna virus related to HBV. Coordinated morphologic and molecular biologic studies on such animal models and on human HCC detected by screening, as for instance in Eskimos, neither complicated by cirrhosis, should elucidate the direction of the evolution of the HCC and the postulated promoting role of the inflammation.     

Prevalence and persistence of antibodies to herpes viruses, Chlamydia pneumoniae and Helicobacter pylori in Alaskan Eskimos: the GOCADAN Study

The prevalence and persistence of antibodies against cytomegalovirus (CMV), herpes simplex virus types 1 (HSV1) and 2 (HSV2), Helicobacter pylori and Chlamydia pneumoniae were determined in Alaskan Eskimos. The study included 610 individuals (mean age 43 +/- 15 years; 45% males) participating in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Archived serum samples and those collected during the GOCADAN study were analysed for antibodies against the above pathogens by ELISA. The current prevalence of antibody seropositivity was 94% to CMV, 90% to HSV1, 38% to HSV2, 80% to H. pylori, and 42% to C. pneumoniae. The persistence of antibodies (in both archived and current samples) against CMV, HSV1 and H. pylori was high (83%, 84% and 67%, respectively) compared with those against HSV2 (26%) and C. pneumoniae (29%). Moreover, the seroconversion rates to these organisms were low. Most individuals acquired CMV, HSV1 and H. pylori antibodies by the age of 24 years (94%, 90% and 72%, respectively), and >50% carried HSV2 and C. pneumoniae antibodies by the age of 45 years. There were gender differences in antibody seropositivity rates. Over 70% of individuals had antibodies to at least three of the five pathogens tested. The study demonstrated the high prevalence and lifelong persistence of multiple antibodies, suggesting chronic infections among Alaskan Eskimos.     

Differential effects of inhaled budesonide and oral prednisolone on serum immunoglobulin G and its subclasses in healthy adult volunteers

Background Glucocorticosteroid (GCS) treatment lowers serum IgG and IgG subclass (IgG-SC) levels, but the minimal dose and duration of administration at which this occurs is not known. Objective The aim of this study was to define the daily dose of a 2-week course of GCS at which IgG(-SC) suppression occurs. Methods The effects of three GCS treatment schemes on serum IgG(-SC) levels in healthy adults were studied in a double-blind, randomized trial. Group I (n= 10) was treated with 40mg oral prednisolone/day, group 2 (n= 10) with 10 mg oral prednisolone/day and group 3 (n= 10) with 3.2 mg inhaled budesonide/day. Blood sampling was performed at baseline and at the end of the 2-week treatment period. Results In group 1, IgGl, IgG2 and lgG3 levels were significantly decreased after treatment, while in group 2 this was only so for IgG3. In both groups, the decrease of total IgG tended towards or just reached significance. In group 3, no statistically significant changes were observed. Conclusion A course of 40mg oral prednisolone/day for 2 weeks induces significant suppression of serum IgG-SC levels; lower doses cause more subtle changes, indicating that GCS-induced IgG-SC suppression is a dose-dependent phenomenon. Short courses of very high doses of inhaled budesonide appear to be devoid of this side-effect.     

Insulin effects on protein synthesis are independent of glucose and energy metabolism

Protein synthesis was accelerated in rat hearts that were provided insulin compared with provision of glucose or pyruvate alone or a mixture of glucose and pyruvate. The faster synthetic rates were accompanied by a reduction in numbers of ribosomal subunits, indicating that peptide chain initiation was accelerated relative to elongation/termination. In hearts supplied glucose, 65% of the maximal effect on protein synthesis was achieved by addition of 1.7 X 10(-10) M insulin, but significant effects on glucose uptake as well as on tissue contents of glucose 6-phosphate and creatine phosphate were obtained only with 7 X 10(-10) M insulin. Addition of glucose to perfusates containing pyruvate did not accelerate protein synthesis, although the glucose 6-phosphate content was raised. Similarly, the stimulatory effects of insulin on protein synthesis in hearts supplied pyruvate did not depend on changes in glucose 6-phosphate content, creatine phosphate/creatine, ATP/ADP, or adenylate energy charge. These studies indicate that insulin accelerated peptide-chain initiation and protein synthesis in rat heart by mechanisms independent of the hormone's effect on glucose or energy metabolism.     

Anger,adiposity, and glucose control in nondiabetic adults: findings from MIDUS II

Anger has been linked to cardiovascular disease, but few studies have examined the relationship between anger and type 2 diabetes. The aim was to investigate associations among different indicators of anger expression, adiposity, and nondiabetic glucose metabolism in a national survey of adults. Participants were 939 adults without diabetes in the Midlife in the US study (MIDUS II). Glucose metabolism was characterized by fasting glucose, insulin, insulin resistance, and glycosylated hemoglobin (HbA_1c). Spielberger’s Anger Expression inventory was used to measure suppressed anger (anger-in), expressed anger (anger-out), and controlled anger (anger-control). We investigated the relationship between anger and glucose metabolism, and whether anger amplified the adverse relationship between body weight distribution (body mass index = BMI and waist-to-hip ratio = WHR) and glucose metabolism. Multivariate-adjusted analyses revealed an association between anger-out and both insulin and insulin resistance. As predicted, anger-in amplified the relationships between BMI and insulin and insulin resistance, while anger-out amplified the association between WHR and insulin and insulin resistance. Low anger-control was associated with higher glucose. None of the three anger measures was significantly associated with HbA_1c. Our findings extend previous research on anger as a potential risk factor for type 2 diabetes by demonstrating that anger expression is associated with clinical indicators of glycemic control, especially among those with pre-existing risk due to obesity and high central adiposity.     

甲状腺激素导致糖代谢异常机制的研究进展

甲状腺激素在体内糖代谢平衡中发挥重要作用,可以通过直接或间接作用于肝脏、骨骼肌、脂肪组织等重要的脏器调节葡萄糖的代谢。本文就甲状腺激素对糖代谢调节及其机制的研究进展及甲状腺疾病与胰岛素抵抗之间的关系进行综述。     

Acute and chronic effects of strenuous exercise on glucose metabolism in isolated, incubated soleus muscle of exercise-trained rats

Male and female Wistar rats were exercise-trained for 6 or 11 weeks respectively, to examine the effects of acute exercise or exercise training per se on insulin-stimulated glucose utilization in soleus muscles isolated and incubated in vitro. The maximal activities of hexokinase and 2-oxoglutarate dehydrogenase were significantly elevated (by greater than 50%) in gastrocnemius muscle of exercise-trained male and female rats, indicating an adaptation to the training regime. No significant differences in any of the variables studied were observed between appropriately matched male and female rats. There were no significant differences in the sensitivity or responsiveness of the rates of lactate formation or glycogen synthesis in soleus muscles isolated from exercise-trained and sedentary animals at rest (exercise-trained animals were studied 40 h after the last exercise bout). On the other hand, acute exercise caused significant changes in soleus muscle glucose metabolism. Basal and insulin-stimulated rates of glycogen synthesis were significantly elevated in soleus muscles incubated from both sedentary and exercise-trained rats immediately after an exercise bout. In addition, the responsiveness of glucose utilization to insulin in soleus muscles from exercise-trained rats was significantly increased after acute exercise. The results indicate that significant changes in the control of glucose metabolism by insulin in soleus muscle occur as a result of an acute exercise bout, while no adaptive changes in insulin sensitivity occur in soleus muscle after exercise training.     

Common set of genes regulates low-density lipoprotein size and obesity-related factors in Alaskan Eskimos: results from the GOCADAN study.

Increasing incidence of cardiovascular disease in traditionally low-risk Alaskan Eskimos is a cause for concern. The purpose of this study was to examine the genetic and environmental correlations of low-density lipoprotein (LDL) subfractions with obesity-related factors in Alaskan Eskimos, using data from the first 954 participants of the Genetics of Coronary Artery Disease in Alaska Natives Study. Estimates of genetic and environmental influence were calculated using a maximum likelihood variance component method implemented in SOLAR. Mean values of weight, body mass index (BMI), and waist were 73.4 +/- 0.5 kg, 27.6 +/- 0.2 kg/m2, and 88.0 +/- 0.4 cm, respectively. LDL, and its small (LDL1), medium (LDL2), and large (LDL3) subfractions, had mean values of 115.8 +/- 1.2 mg/dl, 8.3 +/- 0.4 mg/dl, 19.6 +/- 0.8 mg/dl, and 71.5 +/- 1.5 mg/dl, respectively. Bivariate analysis displayed significant genetic correlations between LDL subfractions and obesity-related factors: LDL1 with BMI (rhoG = 0.67, P < 0.05), waist (rhoG = 0.80, P < 0.001), and subscapular and tricep skinfolds (rhoG = 0.93, P < 0.005, and rhoG = 0.78, P < 0.05, respectively); LDL2 with BMI (rhoG = 0.52, P < 0.05), waist (rhoG = 0.46, P < 0.05), and tricep skinfold (rhoG = 0.60, P < 0.05); and mean LDL size with BMI (rhoG = -0.36), waist (rhoG = -0.42,), and subscapular and tricep skinfolds (rhoG = -0.44 and -0.43, respectively) (P < 0.005). These results show that a common set of genes is influencing LDL size and obesity-related factors in Alaskan Eskimos.     

GLP-1 signalling and effects on glucose metabolism in myocytes from type 2 diabetic patients

Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. The major aims of the present study were i) to investigate the possible extension of this knowledge to myocytes obtained from type 2 diabetic patients, ii) to compare in these patients the response to GLP-1, insulin or the structurally related GLP-1 peptides, exendin (1-39)amide and exendin(9-39)amide, and iii) to explore possible differences in the responsiveness to these agents between normal and diabetic subjects. Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable. Nevertheless, significant differences in glucose transport and metabolism parameters were observed in the diabetic patients vs. normal subjects: in the diabetic patients, basal 2-deoxy-glucose uptake and glycogen synthase a activity were lower, accompanied by a similar increasing effect of GLP-1 or insulin; yet, the basal value for glycogen synthesis was higher, coinciding with a lesser relative increment in response to GLP-1 or insulin.     

The effects of exercise modalities on adiposity in obese rats

OBJECTIVE:

The aim of the present study was to evaluate the effect of both swimming and resistance training on tumor necrosis factor-alpha and interleukin-10 expression, adipocyte area and lipid profiles in rats fed a high-fat diet.

METHODS:

The study was conducted over an eight-week period on Wistar adult rats, who were divided into six groups as follows (n = 10 per group): sedentary chow diet, sedentary high-fat diet, swimming plus chow diet, swimming plus high-fat diet, resistance training plus chow diet, and resistance training plus high-fat diet. Rats in the resistance training groups climbed a vertical ladder with weights on their tails once every three days. The swimming groups swam for 60 minutes/day, five days/week.

RESULTS:

The high-fat diet groups had higher body weights, a greater amount of adipose tissue, and higher tumor necrosis factor-alpha expression in the visceral adipose tissue. Furthermore, the high-fat diet promoted a negative change in the lipid profile. In the resistance training high-fat group, the tumor necrosis factor-alpha expression was lower than that in the swimming high-fat and sedentary high-fat groups. Moreover, smaller visceral and retroperitoneal adipocyte areas were found in the resistance training high-fat group than in the sedentary high-fat group. In the swimming high-fat group, the tumor necrosis factor-alpha expression was lower and the epididymal and retroperitoneal adipocyte areas were smaller compared with the sedentary high-fat group.

CONCLUSION:

The results showed that both exercise modalities improved the lipid profile, adiposity and obesity-associated inflammation in rats, suggesting their use as an alternative to control the deleterious effects of a high-fat diet in humans.