Dairy products on metabolic health: Current research and clinical implications

Dairy products have been thought to have a beneficial role in the metabolic syndrome (MetS). MetS constitutes a cluster of risk factors for an increased mortality, including obesity, impaired glucose homeostasis, hypertension and atherogenic dyslipidemia. Individuals with MetS are also often in a chronic, low-grade inflammatory state. The objective of this review is to examine recent meta-analyses and clinical studies on the association between dairy products consumption and these MetS risk factors. Findings from studies demonstrate that weight loss related to dairy product intake is due to the combination of an energy-restricted diet with consumption of dairy products. Further, a limited number of studies have shown beneficial effects of dairy consumption on plasma lipids, blood pressure, glucose homeostasis or inflammatory and oxidative stress profiles. Overall, this review article suggests that adults should consume at least 2–3 servings of dairy products per day within a well-balanced diet and a healthy lifestyle for metabolic health. Yet, higher dairy product consumption may have additional beneficial effects, but more well-designed intervention studies are needed to ascertain these effects.     

Protein kinase C in enhanced vascular tone in diabetes mellitus

Diabetes mellitus (DM) is a complex syndrome which leads to multiple dysfunctions including vascular disorders. Hyperglycemia is considered to be a key factor responsible for the development of diabetic vascular complications and can mediate their adverse effects through multiple pathways. One of those mechanisms is the activation of protein kinase C (PKC). This important regulatory enzyme is involved in a signal transduction of several vascular functions including vascular smooth muscle contractility. Many studies have shown that hyperglycemia in DM results in oxidative stress. Overproduction of reactive oxygen species (ROS) by different oxidases and the mitochondrial electron transport chain (ETC), advanced glycation end products, polyol pathway flux, and hyperglicemia-induced rising in diacylglycerol (DAG) contribute to the activation of PKC. Activation of endothelial PKC in DM leads to endothelium-dependent vasodilator dysfunction. The main manifestations of this are inhibition of vasodilatation mediated by nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin, and activation of vasoconstriction mediated by endothelin-1 (ET-1), prostaglandin E₂ (PGE₂) and thromboxane A₂ (TXA₂). Activated PKC in DM also increases vascular endothelial growth factor (VEGF) expression and activates NADPH oxidases leading to raised ROS production. On the other hand, PKC in DM is involved in enhancement of vascular contractility in an endothelium-independent manner by inactivation of K⁺ channels and Ca^2 + sensitization of myofilaments in vascular smooth muscle cells. This shows that PKC is a potential therapeutic target for treating vascular diabetic complications.     

Diabetes mellitus and brain atrophy: A computed tomography study in an elderly population

Previous studies have suggested that noninsulin dependent diabetes mellitus (NIDDM) could lead to learning and memory deficits. We studied cognitive performance and computed tomography (CT) findings of the brain in elderly subjects with drug treated NIDDM (n = 12), with diet treated NIDDM (n = 13), and in nondiabetic individuals (ND, n = 59). The cognitive performance (orientation and uptodate knowledge, praxic functions, understanding of speech, expressive speech, memory, general reasoning) did not differ between the groups. The drug treated diabetics had more pronounced central temporal atrophy compared to that in the ND subjects as evidenced by wider right temporal horn (ANCOVA adjusted for age, p = 0.011). The drug treated diabetics (all women) also had wider frontal horns than did the ND women. The CT measures of diet treated diabetics were comparable with those of the ND group. The fasting glucose level was positively correlated with the width of the right temporal horn but not with other CT measures in diabetic subjects. The results suggest that NIDDM and poor glucose control may carry a risk for accelarated brain atrophy in the elderly.     

高血糖症对大鼠血管内皮舒张功能的影响

目的：复制高血糖症动物模型，研究高糖对大鼠血管内皮舒张功能的影响及其机制。方法：采用血管功能检测、组织培养及放射免疫分析方法。结果：①高血糖组血管乙酰胆硷依赖性血管舒张反应明显降低（Ｐ＜００１）；②高血糖组血浆ＮＯ－２含量、主动脉一氧化氮合成酶（ＮＯＳ）活性及环磷酸鸟苷（ｃＧＭＰ）含量明显低于对照组（Ｐ＜００５，Ｐ＜００１）。结论：长期高血糖症可引起血管内皮源性血管舒张因子／一氧化氮（ＥＤＲＦ／ＮＯ）系统出现严重障碍，从而降低了血管舒张功能     

Ubiquitin-protein ligase E3a (UBE3A) as a new biomarker of cardiac hypertrophy in cell models

Cardiac hypertrophy is widely diagnosed in clinical cardiac disorders. The pathophysiology of hypertrophy is complex and multifactorial, a series of molecular and cellular changes are participated, such as activation of different signaling pathways, a switch of fetal gene program in the myocardium, and apoptosis. Some biomarkers have been applied to assess cardiac hypertrophy including atrial natriuretic peptides (ANP), brain/B-type natriuretic peptides (BNP), and α- or β- Myosin Heavy Chain (MHC) in addition to others. Recently, ubiquitin-protein ligase E3A (UBE3A) has been observed to increase in cardiac hypertrophy. Therefore, UBE3A as a new biomarker seems valuable in the clinic. The cardiac hypertrophy is induced in rat-derived heart cell line H9c2 cells by potassium bromate (KBrO3), high glucose (HG), or isoproterenol (Iso), respectively. As an oxidizing agent, KBrO3 increased cell size at concentrations less than 250 μM. Similarly, HG and Iso also induced cardiac hypertrophy in H9c2 cells. Interestingly, each kind of the cell models promoted the gene expression of the well-known biomarkers of cardiac hypertrophy including atrial natriuretic peptides (ANP) and brain/B-type natriuretic peptides (BNP). Additionally, UBE3A is also raised with the signals involved in cardiac hypertrophy such as calcineurin and nuclear factor of activated T-cells (NFAT) determined using Western blots. KBrO3 increased the protein levels of these signals and the specific inhibitor, such as cyclosporine A and tacrolimus, attenuated the signaling in H9c2 cells at concentrations sufficient to inhibit calcineurin in addition to the reduction of mRNA levels of UBE3A, similar to ANP or BNP. Moreover, HG or Iso also significantly increased protein levels of UBE3A in H9c2 cells. Taken together, we provided a new view that UBE3A is markedly raised in cardiac hypertrophy using various cell models, mainly through the activation of the calcineurin/NFAT signaling pathway in H9c2 cells. Therefore, UBE3A could be developed as a new biomarker in the diagnosis of cardiac hypertrophy.     

中国成年人肉类食物摄入与代谢综合征的相关性研究

目的 分析我国≥18岁成年人肉类食物摄入量与MS患病的关系。方法 2010－2012年中国居民营养与健康状况监测中34 923名≥18岁完成膳食调查并具有完整体检及血糖、血脂检测结果的成年人作为研究对象,根据2013年中华医学会糖尿病分会提出的中国人的MS诊断标准,经复杂抽样加权处理后,计算患病率与成年人肉类摄入量间关系。结果 成年居民人均肉类食物摄入量为94.8 g/d。平均每日摄入量在100～199 g/d的人群MS、腹型肥胖和高血糖的患病率最低。随着摄入量的增加,男性MS患病率显著增加,且摄入量≥300 g/d的人群发生MS的风险显著高于低摄入水平人群,调整后患病率比（PR）为1.46（95% CI：1.14～1.87）,但未在摄入量≥300 g/d的女性人群中观察到相似趋势。结论 中国成年人群摄入适量肉类发生MS的风险较低。     

老年合并糖尿病的大肠癌52例治疗探讨

目的;探讨老年高血糖大肠癌的外科治疗措施。方法：１９９２年至１９９８年外科治疗的５２例老年大肠癌伴高血糖患者作回顾性分析。结果：９２例患者均行择期手术,术后并发症发生率：吻合口瘘占７．７％（４／５２）,骶前间隙积脓３．９％,切口感染２１．８％肺部感染,腹腔脓肿均为３．０％,无酮症酸酸中毒。术后平均住院１９．５ｄ,无手术死亡病例。结论;老年高血糖大肠癌只有围手术期严格控制血糖,选择合理术式完全可以达     

Metformin prevents the impairment of endothelium-dependent vascular relaxation induced by high glucose challenge in rabbit isolated perfused kidneys

High glucose concentrations are involved in the development of diabetic-associated vascular complications. We have previously reported that acute high glucose challenge, corresponding to post-prandial glycemia levels observed in patients with type 2 diabetes, blunts ACh-induced endothelium-dependent relaxation of the renal circulation of non-diabetic rabbits. Isolated perfused kidneys from non-diabetic rabbits were acutely exposed (3 h) to normal (5.5 mM—control group) or high (15 mM) D-glucose concentrations in the presence or absence of a continuous infusion of metformin (20 or 100 M). Renal vascular reactivity was evaluated with endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasodilating agents. ACh-induced maximal renal vasodilation was reduced by high glucose infusion (15 mM) in comparison to the control group (25±3% and 41±3% respectively; P<0.01), being restored to 41±4% and 43±2% by a simultaneous 3-h infusion of 20 or 100 M of metformin respectively (P>0.05). Perfusion of the kidneys with the angiotensin II-converting enzyme inhibitor captopril (10 M) also significantly prevented the deleterious effects of high glucose challenge in the renal circulation. The use of a continuous infusion of -nitro-L-arginine methyl ester (L-NAME, 100 M) did not affect the protective effect of metformin in the renal circulation (39±4%; P>0.05), while tetraethylammonium (TEA, 10 mM) partially blunted this effect (33±4, P<0.01). Renal vasodilation induced by SNP was not modified by simultaneous infusion of high glucose and/or metformin. It is concluded that the impairment of ACh-induced endothelium-dependent renal vasodilation observed after acute exposure to high glucose concentrations is abolished by metformin administration. These alterations of renal vascular reactivity can be accounted for, at least in part, by the activation of the renal renin-angiotensin system during hyperglycemia. The protective effects of metformin present some EDHF-dependent component and are not related to metabolic pathways dependent on nitric oxide.     

High Glucose Induces Connective Tissue Growth Factor Expression and Extracellular Matrix Accumulation in Rat Aorta Vascular Smooth Muscle Cells Via Extracellular Signal-Regulated Kinase 1/2

Connective tissue growth factor (CTGF) is a potent pro-fibrotic factor, which is implicated in fibrosis through extracellular matrix (ECM) induction in diabetic cardiovascular complications. It is an important downstream mediator in the fibrotic action of transforming growth factor β (TGFβ) and is potentially induced by hyperglycemia in human vascular smooth muscle cells (VSMCs). Therefore, the goal of this study is to identify the signaling pathways of CTGF effects on ECM accumulation and cell proliferation in VSMCs under hyperglycemia. We found that high glucose stimulated the levels of CTGF mRNA and protein and followed by VSMC proliferation and ECM components accumulation such as collagen type 1, collagen type 3 and fibronectin. By depleting endogenous CTGF we showed that CTGF is indispensable for the cell proliferation and ECM components accumulation in high glucose-stimulated VSMCs. In addition, pretreatment with the MEK1/2 specific inhibitors, PD98059 or U0126 potently inhibited the CTGF production and ECM components accumulation in high glucose-stimulated VSMCs. Furthermore, knockdown with ERK1/2 MAPK siRNA resulted in significantly down regulated of CTGF production, ECM components accumulation and cell proliferation in high glucose-stimulated VSMCs. Finally, ERK1/2 signaling regulated Egr-1 protein expression and treatment with recombinant CTGF reversed the Egr-1 expression in high glucose-induced VSMCs. It is conceivable that ERK1/2 MAPK signaling pathway plays an important role in regulating CTGF expression and suggests that blockade of CTGF through ERK1/2 MAPK signaling may be beneficial for therapeutic target of diabetic cardiovascular complication such as atherosclerosis.     

Pollution by metals: Is there a relationship in glycemic control?

There are evidences of environmental pollution and health effects. Metals are pollutants implicated in systemic toxicity. One of the least studied effects, but which is currently becoming more important, is the effect of metals on glycemic control. Metals have been implicated as causes of chronic inflammation and oxidative stress and are associated to obesity, hyperglycemia and even diabetes. Arsenic, iron, mercury, lead, cadmium and nickel have been studied as a risk factor for hyperglycemia and diabetes. There is another group of metals that causes hypoglycemia such as vanadium, chromium, zinc and magnesium by different mechanisms. Zinc, magnesium and chromium deficiency is associated with increased risk of diabetes. This review summarizes some metals involved in glycemic control and pretends to alert health professionals about considering environmental metals as an important factor that could explain the poor glycemic control in patients. Further studies are needed to understand this poorly assessed problem.