Hypoglycemic effect of whole grain diet in C57BL/KsJ-db/db mice by activating PI3K/Akt and AMPK pathways

Food Science and Biotechnology - Type II diabetes mellitus (T2DM), characterized by abnormal blood glucose level, is a metabolic disease caused by pancreatic β-cell dysfunction and insulin...     

Evidences for diabetes and insulin mimetic activity of medicinal plants: Present status and future prospects

Diabetes mellitus (DM) is a considerable systemic metabolic disorder to exhibit various metabolic and cardiovascular disorders, mainly hyperglycemia. The global projected estimate of diabetes in 2030 will be about 439 million adults, out of which 300 million expected are of type-2 diabetes mellitus (T2DM). The present knowledge revealed responsible factors, occurrence and mechanism of these factors involved in the DM diseases. Hence, the aim of this review is to address and summarize the causes, plant resources, importance, present status and future programmes for diabetes control. The present review answers the contemporary present questions raised in the scientific field on DM. Two major problems are explained in detail about the autoimmune attack or dysfunction of β-cell and insulin resistance involved for Type 1 and Type 2 DM, respectively. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, many preferred herbal formulations due to lesser side effects and low cost. For this reason still it is getting increased attention in searching antidiabetic medicinal plants for hot research and to develop targeted medicine. Recurrence of islet autoimmunity lesson from pancreatic islet cell transplantation to cure T1D was outlined. With these highlights, the review summarizes the current knowledge on diabetes occurrence, factors (environmental and genetics), and types (I, II, gestation, and secondary DM), antidiabetic plants, sources for insulin mimetic plant principle compounds and their target mechanism with current and future trusted research areas for controlling of DM.     

槲皮素通过Nrf2通路对糖尿病大鼠胰腺氧化损伤的拮抗作用机制

目的：探讨槲皮素是否通过核因子E2相关因子2（nuclear factor erythroid 2-related factor 2, Nrf2）通路拮抗糖尿病大鼠胰腺氧化损伤。方法：选取SPF级SD大鼠48 只,随机选取10 只大鼠作为正常对照组,其余38 只大鼠饲喂高脂饲料联合注射30 mg/kg mb链脲佐菌素建立2型糖尿病（type 2 diabetes mellitus,T2DM）模型。以大鼠随机血糖浓度不低于16.7 mmol/L作为造模成功判断标准,按血糖浓度分层将大鼠随机分为T2DM模型组、低剂量槲皮素（L-QU）、高剂量槲皮素（H-QU）干预组,每组10 只,连续灌胃12 周。测定大鼠胰腺组织匀浆液的氧化损伤和抗氧化指标,运用Western Blot、实时定量聚合酶链式反应测定Nrf2、血红素氧合酶1（heme oxygenase 1,HO-1）、谷胱甘肽硫转移酶（glutathione S-transferase,GST）、NADP(H):醌氧化还原酶1（NADP(H):quinone oxido-reductase 1,NQO1）蛋白及其mRNA表达量。结果：与T2DM模型组相比,低、高剂量槲皮素干预显著降低了大鼠血糖浓度和胰腺丙二醛含量（P＜0.05）,减轻胰岛素抵抗,显著提高超氧化物歧化酶等抗氧化酶活力（P＜0.05）,Nrf2以及下游抗氧化酶HO-1、NQO1的蛋白含量和mRNA表达量均显著上升（P＜0.05）。结论：槲皮素可能是通过激活胰腺组织Nrf2信号通路,上调下游抗氧化酶表达,进而减轻T2DM大鼠胰腺氧化损伤,改善胰岛素抵抗,调节血糖水平,从而发挥防治糖尿病的作用。     

低剂量酒精摄入对不同性别2型糖尿病小鼠的影响

为探究低剂量酒精摄入对不同性别2型糖尿病（T2DM）小鼠影响的差异性及可能机制,采用链脲佐菌素（STZ）处理高脂高糖饲料喂养的小鼠构建T2DM模型,以灌胃200 mg/（kg·d）二甲双胍的T2DM小鼠为阳性对照,连续灌胃低剂量酒精（0.033 mL/d）30 d后,测定不同性别小鼠的糖脂代谢相关指标和胰腺组织氧化应激水平,并观察胰腺组织中胰岛的损伤、测定胰岛素的表达情况。结果表明,连续30 d摄入低剂量酒精可加重T2DM雄性小鼠糖脂代谢紊乱及胰腺组织中胰岛损伤,降低胰岛素表达量,上调T2DM雄性小鼠胰腺组织氧化应激水平,但并未对T2DM雌性小鼠产生显著影响,推测胰腺组织氧化应激水平的差异性影响可能是低剂量酒精对不同性别T2DM小鼠产生差异影响的主要机制之一。     

维生素C防治2型糖尿病研究进展

2型糖尿病（T2DM）是由胰岛素缺乏和胰岛素抵抗引起的复杂代谢紊乱性疾病。维生素C（V_C）是人体必需的营养素,是众所周知的抗氧化剂,可保护细胞免受氧化应激的伤害。T2DM患者的氧化应激状态对并发症的发生发展起重要作用,适量补充V_C可降低T2DM的发病风险。V_C与T2DM及其并发症密切相关,T2DM患者血浆V_C水平普遍偏低,且血浆V_C水平与T2DM的患病风险呈负相关;补充V_C可以改善胰岛素抵抗、改善炎症状态,同时可延缓糖尿病肾病的发生发展和心血管的发生风险,但在糖尿病牙周疾病方面并没有明显的改善作用。本文对V_C与T2DM发生发展中的作用予以综述,旨在为T2DM的防治提供一定的参考。     

Advanced glycosylation end products and nutrition--a possible relation with diabetic atherosclerosis and how to prevent it

ABSTRACT:  Advanced glycosylation end product (AGE) levels are elevated in diabetic patients and may contribute to the excessive cardiovascular disease in this population, promoting oxidant stress and chronic vascular inflammation. AGEs in people with diabetes mellitus are formed mainly by protein and lipid glucosylation in an environment of chronic hyperglycemia and also by prolonged thermal food processing (diet derived AGEs). This brief review summarizes current literature about food derived AGEs and their relationship with diabetic vascular disease and supports the importance of low AGE diet as an essential preventive or therapeutic intervention against atheromatosis progress.     

Consumption of barley β‐glucan ameliorates fatty liver and insulin resistance in mice fed a high‐fat diet

Consumption of a diet high in barley β‐glucan (BG) has been shown to prevent insulin resistance. To investigate the mechanism for the effects of barley BG, three groups of male 7‐wk‐old C57BL/6J mice were fed high‐fat diets containing 0, 2, or 4% of barley BG for 12 wk. The 2% BG and 4% BG groups had significantly lower body weights compared with the 0% BG group. The 4% BG group demonstrated improved glucose tolerance and lower levels of insulin‐resistance index and glucose‐dependent insulinotropic polypeptide. Consumption of the BG diet decreased hepatic lipid content. Mice on the BG diet also demonstrated decreased fatty acid synthase and increased cholesterol 7α‐hydroxylase gene expression levels. The BG diet promoted hepatic insulin signaling by decreasing serine phosphorylation of insulin receptor substrate 1 and activating Akt, and it decreased mRNA levels of glucose‐6‐phosphatase and phosphoenolpyruvate carboxykinase. In summary, consumption of BG reduced weight gain, decreased hepatic lipid accumulation, and improved insulin sensitivity in mice fed a high‐fat diet. Insulin signaling enhanced due to the expression changes of glucose and lipid metabolism genes by BG consumption. Consumption of barley BG could be an effective strategy for preventing obesity, insulin resistance, and the metabolic syndrome.     

Probiotics intake and metabolic syndrome: A proposal

Probiotics are practical tools to provide the modulation of microbiota. The ingestion of food or ingredients containing anti-inflammatory activity components as probiotics should be useful in obesity control and associated co-morbidities treatment. Metabolic syndrome is a metabolic dysfunction associated with visceral obesity and insulin resistance, in which the alterations in host-microbiota interactions play an important role. Besides diet and physical activity, new strategies are necessary to control metabolic syndrome, and as consequence improving quality of life. This article revises the actual knowledge concerning probiotic intake and obesity as a proposal to control metabolic syndrome.     

粗粮速食米替代高脂饮食对2型糖尿病小鼠糖脂代谢的影响

粗粮速食米（instant rice with added coarse grain，IR/CG）是一种新型的粗粮制品，既具有自热米饭食用方便的特点，又具有粗粮谷物的营养价值，但其产生的健康影响并不明确，因此本研究通过高脂饮食（high fat diet，HFD）联合链脲佐菌素腹腔注射诱导小鼠产生糖尿病，探究IR/CG对2型糖尿病（type 2 diabetes mellitus，T2DM）小鼠糖脂代谢的作用。通过IR/CG与高脂饲料不同比例混合制备小鼠饲料，低、中、高剂量（25%（质量分数，下同）、50%、75% IR/CG）饲料以及100% IR/CG饲料分别记作IR/CG-L、IR/CG-M、IR/CG-H及IR/CG，利用上述饲料喂养小鼠，并与基础饲料、高脂饲料喂养的小鼠（分别记作Control、Model组）进行生理、生化指标等的比较。在饮食干预期间测定小鼠体质量、空腹血糖浓度、摄食量及葡萄糖耐量；IR/CG饮食干预4 周后，计算小鼠脏器系数，对小鼠肝脏、胰腺进行苏木精-伊红染色，测定小鼠空腹胰岛素水平、血糖血脂相关指标，并测定小鼠促炎细胞因子水平。结果显示，IR/CG的摄入能够不同程度改善T2DM小鼠高血糖血脂水平，其中IR/CG-H、IR/CG组改善效果较为显著。此外，IR/CG-H、IR/CG能够显著改善小鼠胰岛素抵抗现象，减少胰岛素分泌、降低胰高血糖素及糖基化血红蛋白水平，减轻小鼠炎症状态。通过对肝脏、胰腺的脏器指数及病理学切片分析发现，IR/CG干预能够有效减轻小鼠肝脂肪变性，部分恢复胰岛结构。上述结果表明IR/CG替代HFD对T2DM小鼠具有显著的调节血糖血脂作用，本研究能为粗粮自热米饭产品及粗粮功能性食品的开发提供理论依据。     

Impact of whole cereals and processing on type 2 diabetes mellitus: a review

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) has been increasing throughout the world. The cereals, as the high carbohydrate food and dominant portion of diet, have crucial impacts on glycemic control, especially for T2DM. Both components in whole cereals and processing are closely related to their glycemic response. The consumption of whole cereals is shown to reduce the risk of T2DM. The starch characteristic of cereal determines its hydrolysis rate and glycemic response. The soluble and insoluble dietary fiber, phenolic compounds, and other bioactive constituents may slow down the starch hydrolysis. Besides, they have other physiological mechanisms in regulation of T2DM, such as amelioration of lipid disorder, antioxidant, anti-inflammation, and regulation of gut microbiota, which contribute to further improvement of metabolic symptoms. Cereals are subjected to processing before consumption, which is involved in mechanical force, bioprocessing, thermal treatment, and cooling. The processing induces changes in nutritional composition and physical structure compared to the raw kernels. The key influences of processing on glycemic response are the starch gelatinization and starch retrogradation. However, physical structure of cereal and interactions among starch and other compounds greatly contribute to various glycemic responses of cereal products. This review highlights recent findings on the influences of both bioactive constituents and processing on the antidiabetic effects and physiological properties of cereals.     

Antioxidant potential of mate tea (Ilex paraguariensis) in type 2 diabetic mellitus and pre-diabetic individuals

The effect of long-term mate tea (Ilex paraguariensis) consumption on the oxidative stress biomarkers of type 2 diabetic mellitus and pre-diabetic individuals was investigated. A 60-day intervention pilot study where 11 T2DM and 11 pre-diabetic volunteers ingested 1 L/day of mate tea was carried out. Ferric reducing antioxidant power (FRAP), erythrocyte reduced glutathione (GSH), serum lipid hydroperoxides (LOOH) using ferrous oxidation-xylenol orange (FOX2), advanced glycation end-products (AGEs), and glycaemic and lipid profiles were assessed at baseline and after 20, 40, and 60 days of intervention. Mate tea consumption promoted a significant increase of GSH concentration and a decrease of LOOH levels in T2DM and pre-diabetic subjects. In addition, GSH concentration was inversely correlated with LOOH in T2DM and pre-diabetic individuals and with AGEs in T2DM subjects. No correlations between glycaemic and lipid profiles with oxidative stress biomarkers were found. Thus, ingestion of mate tea attenuated oxidative stress in T2DM and pre-diabetic subjects, which may prevent diabetes complications.     

No Adverse Programming by Post‐Weaning Dietary Fructose of Body Weight,Adiposity, Glucose Tolerance,or Metabolic Flexibility

1 Scope

Metabolic programming can occur not only in the perinatal period, but also post‐weaning. This study aims to assess whether fructose, in comparison to glucose, in the post‐weaning diet programs body weight, adiposity, glucose tolerance, metabolic flexibility, and health at adult age.

2 Methods and results

Three‐week‐old male and female C57BL6/JRccHsd mice are given an intervention diet with 32 energy percent (en%) glucose or fructose for only 3 weeks. Next, all animals are switched to the same 40 en% high fat diet for 9 weeks. Neither body weight nor adiposity differs significantly between the animals fed with glucose or fructose diets at any point during the study in both sexes. Glucose tolerance in adulthood is not affected by the post‐weaning diet, nor are activity, energy expenditure, and metabolic flexibility, as measured by indirect calorimetry. At the end of the study, only in females fasting serum insulin levels and HOMA‐IR index are lower in post‐weaning fructose versus glucose diet (p = 0.02), without differences in pancreatic β‐cell mass.

3 Conclusions

Our present findings indicate no adverse programming of body weight, adiposity, glucose tolerance, and metabolic flexibility by dietary (solid) fructose in comparison to glucose in the post‐weaning diet in mice.     

D-松醇复配Mn2+对2型糖尿病大鼠的降血糖作用及其机制的研究

目的:研究D-松醇复配Mn2+对2型糖尿病大鼠的降血糖作用并探讨其作用机制。方法:选用SPF级雄性大鼠进行实验,高糖高脂饲料喂养配合注射链脲佐菌素(STZ)诱导建立2型糖尿病(T2DM)模型。实验动物分为空白对照组、模型对照组、阳性对照组、D-松醇组和低、中、高复配Mn2+组,灌胃期间每周定时测体重和空腹血糖(FBG),4周后测定口服葡萄糖耐量(OGTT)和胰岛素耐量(ITT),5周后处死并对其糖化血清蛋白(GSP)、空腹血清胰岛素(FINS)等生理生化指标进行测定,计算胰岛素敏感性指数(ISI)和胰岛β细胞功能指数(HOMA-β)。并采用实时荧光全定量分析(RT-PCR)实验检测AMPK信号通路相关基因mRNA表达水平。结果:与模型对照组相比,剂量组均可显著性降低T2DM大鼠空腹血糖值(p<0.05),高剂量复配组血糖值极显著降低(p<0.01)。此外,与D-松醇组相比,高剂量复配组的FINS和GSP极显著降低(p<0.01)。与模型对照组相比,ISI-1、ISI-2和AMPKα-2基因mRNA表达水平显著上调(p<0.05),且高剂量组与D-松醇组相比极显著性上调(p<0.01)。高剂量复配组AMPKα-1和GLUT4基因mRNA表达水平显著上调(p<0.05),PGC-1α、PEPCK和G6Pase基因mRNA表达水平显著下调(p<0.05)。结论:D-松醇复配Mn2+提高了T2DM大鼠对葡萄糖的耐受能力,缓解胰岛素抵抗症状,提高机体对胰岛素的敏感性,其作用机制可能涉及AMPK参与的抑制糖异生等生化调控过程起到降血糖作用。     

Effects of timing of palmitic acid supplementation during early lactation on nutrient digestibility,energy balance,and metabolism of dairy cows

The objective of our study was to evaluate the effects of timing of palmitic acid (C16:0) supplementation during early lactation on nutrient digestibility, energy intake and balance, and metabolic responses of dairy cows. Fifty-two multiparous cows were used in a randomized complete block design experiment. During the fresh (FR) period (1–24 d in milk) cows were assigned to either a control diet containing no supplemental fat (CON) or a C16:0-supplemented diet [PA; 1.5% of diet dry matter (DM)]. During the peak (PK) period (25–67 d in milk) cows were assigned to either a CON diet or a PA diet (1.5% of diet DM) in a 2 × 2 factorial arrangement of treatments considering the diet that they received during the FR period. During the FR period, compared with CON, PA increased DM digestibility by 3.0 percentage units and neutral detergent fiber (NDF) digestibility by 4.4 percentage units, and the increase in these variables was consistent over time. Although PA did not affect 18-carbon fatty acid (FA) digestibility, it decreased 16-carbon FA digestibility by 10.8 percentage units and total FA digestibility by 4.7 percentage units compared with CON. We observed a tendency for an interaction between treatment and time for total FA digestibility and 16-carbon FA digestibility due to the difference in FA digestibility between PA and CON reducing over time. Compared with CON, PA increased digestible energy intake by 3.9 Mcal/d, metabolizable energy intake by 3.5 Mcal/d, and net energy for lactation intake by 2.5 Mcal/d. The PA diet also increased milk energy output, negative energy balance, and plasma nonesterified fatty acid concentration and reduced plasma insulin concentration. We also observed a tendency for an interaction between treatment and time for energy balance due to cows receiving the PA treatment being in a greater negative energy balance over time. During the PK period, PA increased DM digestibility by 2.9 percentage units and NDF digestibility by 3.5 percentage units compared with CON. Although PA decreased 16-carbon FA digestibility by 7.0 percentage units, PA did not affect 18-carbon FA digestibility or total FA digestibility. Feeding PA during the PK period increased energy intake and milk energy output and did not affect energy balance. In conclusion, feeding a C16:0 supplement to early-lactation cows consistently increased DM and NDF digestibilities and energy intake compared with a control diet containing no supplemental fat. Feeding C16:0 markedly increased milk energy output in both the FR and PK periods but increased negative energy balance only in the FR period.     

Effect of diet therapy on status of hemocoagulation and fibrinolysis in type 2 diabetes patients

The changes in parameters of blood coagulation and the fibrinolytic system in 60 patients with type 2 diabetes mellitus was studied. We conclude what the non insulin depended diabetes mellitus is associated with disturbances in hemostatic and fibrinolytic systems that could contribute to the development of diabetic vascular disease. Besides favorable influence to a clinical picture of disease universal normalizing influence of traditional diet therapy on parameters of coagulation and the fibrinolytic system. Our results show that diet therapy improve metabolic control in type 2 diabetic patients could reflect a reduces thrombotic potential and decreased cardiovascular risk.     

Glycolaldehyde‐modified β‐lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE‐expressing human cell lines

Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde‐modified β‐lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X‐114 (TX‐114). Affinity column‐purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde‐modified AGEs purified by extraction with TX‐114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin‐like activity was demonstrated in the detergent phase after extraction with TX‐114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde‐modified AGEs are unable to induce inflammatory signaling in receptor for AGE‐expressing cells. The observed cell‐activating activity can be ascribed to an endotoxin‐like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.     

多酚对食源性晚期糖基化终末产物及其诱导的相关疾病的抑制作用研究进展

晚期糖基化终末产物通过引起活性氧产生、激活氧化应激反应从而诱发各种慢性代谢性疾病，如糖尿病性肾病、阿尔茨海默病、动脉粥样硬化和骨关节炎等。因此，晚期糖基化终末产物被认为是一种促进宿主细胞死亡和器官损伤的强毒性分子。多酚是自然界中常见的一种次生代谢产物，其结构多样，具有抗氧化、抗炎、抗菌等多种生物活性。天然产物多酚可通过捕获自由基、阻断炎症信号通路和与微生物相互作用等多种机制减少晚期糖基化终末产物的产生并抑制相关疾病的发生。本文综述了多酚对晚期糖基化产物及相关疾病的抑制作用，以期为多酚抑制晚期糖基化产物的进一步研究提供科学参考。     

Gut microbiota and probiotics: Focus on diabetes mellitus

The characterization of gut microbiota has become an important area of research in several clinical conditions, including type 2 diabetes (T2DM). Changes in the composition and/or metabolic activity of the gut microbiota can contribute to human health. Thus, this review discusses the effects of probiotics and gut microbiota on metabolic control in these individuals. Relevant studies were obtained from electronic databases such as PubMed/Medline and ISI Web of Science. The main probiotics used in these studies belonged to the genera Lactobacillus and Bifidobacterium. The authors found seven randomized placebo-controlled clinical trials and 13 experimental studies directly related to the effect of probiotics on metabolic control in the context of T2DM. The hypothesis that gut microbiota plays a role in the development of diabetes indicates an important beginning, and the potential of probiotics to prevent and reduce the severity of T2DM is better observed in animal studies. In clinical trials, the use of probiotics in glycemic control presented conflicting results, and only few studies have attempted to evaluate factors that justify metabolic changes, such as markers of oxidative stress, inflammation, and incretins. Thus, further research is needed to assess the effects of probiotics in the metabolism of diabetic individuals, as well as the main mechanisms involved in this complex relationship.