Effects of Cyclo-His-Pro-enriched yeast hydrolysate on blood glucose levels and lipid metabolism in obese diabetic ob/ob mice

BACKGROUND/OBJECTIVES

We examined the hypoglycemic and anti-hyperlipidemic effect of yeast hydrolysate (YH) enriched with Cyclo-His-Pro (CHP) in the C57BL/6J ob/ob mouse model.

MATERIALS/METHODS

Mice were separated into 4 groups (8 mice/group) on the basis of blood glucose and body weight: WT control, lean mice given vehicle; ob/ob control, ob/ob mice given vehicle; YH-1, ob/ob mice given 0.5 g/kg of YH; YH-2, ob/ob mice given 1 g/kg of YH. YH in saline or vehicle was administered orally in the same volume every day for 3 weeks.

RESULTS

Mice treated with YH (0.5 and 1 g/kg) for 3 weeks displayed a significant reduction in overall body weight gain and perirenal and epididymal adipose tissue weight compared to the ob/ob control group. Additionally, high-density lipoprotein (HDL) cholesterol, glucose, and atherogenic indexes were significantly decreased in the blood of YH-1 and YH-2 groups compared to the ob/ob control. In ob/ob mice, YH administration significantly improved glucose tolerance and blood insulin levels. These data indicate that YH treatment produces potent hypoglycemic and anti-hyperlipidemic effects by controlling body weight, fat mass, blood lipid, insulin levels, and glucose tolerance.

CONCLUSION

YH could potentially be used as a treatment option for diabetes and hyperlipidemia. The CHP-enriched YH may be a promising strategy in the development of hypoglycemic peptide nutraceuticals.     

Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice

Metabolic dysregulation (e.g., hyperglycemia, hyperinsulinemia, hyperlipidemia, etc.) is a hallmark of obesity-related diseases such as insulin resistance, type 2 diabetes, and fatty liver disease. In this study, we assessed whether dietary capsaicin attenuated the metabolic dysregulation in genetically obese diabetic KKAy mice, which have severe diabetic phenotypes. Male KKAy mice fed a high-fat diet for 2 weeks received a 0.015% capsaicin supplement for a further 3 weeks and were compared with nonsupplemented controls. Dietary capsaicin markedly decreased fasting glucose/insulin and triglyceride levels in the plasma and/or liver, as well as expression of inflammatory adipocytokine genes (e.g., monocyte chemoattractant protein-1 and interleukin-6) and macrophage infiltration. At the same time expression of the adiponectin gene/protein and its receptor, AdipoR2, increased in adipose tissue and/or plasma, accompanied by increased activation of hepatic AMP-activated protein kinase, a marker of fatty acid oxidation. These findings suggest that dietary capsaicin reduces metabolic dysregulation in obese/diabetic KKAy mice by enhancing expression of adiponectin and its receptor. Capsaicin may be useful as a dietary factor for reducing obesity-related metabolic dysregulation.     

Dietary epicatechin promotes survival of obese diabetic mice and Drosophila melanogaster

The lifespan of diabetic patients is 7-8 y shorter than that of the general population because of hyperglycemia-induced vascular complications and damage to other organs such as the liver and skeletal muscle. Here, we investigated the effects of epicatechin, one of the major flavonoids in cocoa, on health-promoting effects in obese diabetic (db/db) mice (0.25% in drinking water for 15 wk) and Drosophila melanogaster (0.01-8 mmol/L in diet). Dietary intake of epicatechin promoted survival in the diabetic mice (50% mortality in diabetic control group vs. 8.4% in epicatechin group after 15 wk of treatment), whereas blood pressure, blood glucose, food intake, and body weight gain were not significantly altered. Pathological analysis showed that epicatechin administration reduced the degeneration of aortic vessels and blunted fat deposition and hydropic degeneration in the liver caused by diabetes. Epicatechin treatment caused changes in diabetic mice that are associated with a healthier and longer lifespan, including improved skeletal muscle stress output, reduced systematic inflammation markers and serum LDL cholesterol, increased hepatic antioxidant glutathione concentration and total superoxide dismutase activity, decreased circulating insulin-like growth factor-1 (from 303 ± 21 mg/L in the diabetic control group to 189 ± 21 mg/L in the epicatechin-treated group), and improved AMP-activated protein kinase-α activity in the liver and skeletal muscle. Consistently, epicatechin (0.1-8 mmol/L) also promoted survival and increased mean lifespan of Drosophila. Therefore, epicatechin may be a novel food-derived, antiaging compound.     

Effects of malted barley extract and banaba extract on blood glucose levels in genetically diabetic mice

This study investigated the therapeutic effects of a malted barley extract (MBE) and of banaba extract on blood glucose, insulin, and other biochemical parameters in genetically diabetic mice (C57BL/KsJ(-) m (+/+) Lepr (db)). The mice were divided into three groups-control, MBE, and banaba-according to supplementation. Both MBE and banaba extracts were orally administered to the animals for 12 weeks at doses of 62.5 mg/kg of body weight and 0.8 mg/kg of body weight, respectively. The body and organ (liver and kidney) weights were not different among groups. Fasting blood glucose was significantly lower in the MBE group compared with the control (P < .05). Hemoglobin A1c content was significantly lower in the MBE group compared with either the control or banaba group (P < .05). There was no significant difference in the serum insulin level among groups. The glucose-6-phosphatase activity in kidney was significantly lower in both the MBE and banaba groups compared with the control group (P < .05), but there was no significant difference between the MBE and banaba groups. Therefore, the results of this study demonstrate that MBE alleviates many of the symptoms of diabetes in genetically obese mice and may offer promise as a therapeutic supplement for the normalization of blood glucose levels in humans with hyperglycemia and have beneficial effects in patients with non-insulin-dependent diabetes mellitus.     

Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice

Purpose

Although several researches have demonstrated that rooibos extract has hypoglycemic effect, the role of aspalathin, a main polyphenol in the extract, remains unclear. Our aims were to find specific mechanisms for anti-diabetic action of aspalathin employing a rat skeletal muscle-derived cell line (L6 myocytes) and a rat-derived pancreatic β-cell line (RIN-5F cells) and to investigate its effect in type 2 diabetic model ob/ob mice.

Methods

We investigated in vitro the effect of aspalathin on the glucose metabolism through the studies on molecular mechanisms of glucose uptake using cultured L6 myotubes. We also measured the antioxidative ability of aspalathin against reactive oxygen species (ROS) generated by artificial advanced glycation end product (AGE) in RIN-5F cells. In vivo, ob/ob mice were fed 0.1 % aspalathin-containing diet for 5 weeks, and the effect of aspalathin on fasting blood glucose level, glucose intolerance, and hepatic gene expression was studied.

Results

Aspalathin dose dependently increased glucose uptake by L6 myotubes and promoted AMP-activated protein kinase (AMPK) phosphorylation. Aspalathin enhanced GLUT4 translocation to plasma membrane in L6 myoblasts and myotubes. In RIN-5F cells, aspalathin suppressed AGE-induced rises in ROS. In vivo, aspalathin significantly suppressed the increase in fasting blood glucose levels and improved glucose intolerance. Furthermore, aspalathin decreased expression of hepatic genes related to gluconeogenesis and lipogenesis.

Conclusions

Hypoglycemic effect of aspalathin is related to increased GLUT4 translocation to plasma membrane via AMPK activation. In addition, aspalathin reduces the gene expression of hepatic enzymes related to glucose production and lipogenesis. These results strongly suggest that aspalathin has anti-diabetic potential.     

Dietary supplementation with bean extract improves lipid profile in overweight and obese subjects

The aim of this study was to evaluate the long-term effects of a dietary supplementation of bean extract on serum lipids, nutritional parameters, and fat excretion in feces.Sixty-two overweight and obese (body mass index > 25 kg/m(2)) volunteers were randomized to receive the dietary supplement (n = 31, supplement group) or the placebo (n = 31, placebo group). There were 41 women and 21 men, ages 22 to 66 years. Two capsules of a dietary supplement or a placebo were administered three times daily for 3 mo. The supplement group was then invited to participate in an open-label study for 9 mo. Twenty-four subjects (7 men and 17 women) were randomized to receive two or four capsules of the supplement three times daily. Lipids and nutritional blood parameters were measured at baseline, after 3 mo, and at 12 mo. Excretion of fat in feces was measured.At 3 mo, reduction in serum concentration of cholesterol was found in the supplement group but not in the placebo group. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triacylglycerols in serum did not change in either group. In the 9-mo open-label study, no further reduction in serum cholesterol was observed. Low-density lipoprotein and the ratio of low- to high-density lipoprotein decreased, whereas triacylglycerols remained unchanged. Serum vitamin B12 and folic acid decreased but remained within the normal range. Ferritin and albumin in serum remained unchanged. No differences were observed in serum lipids and nutritional parameters between groups. The bean extract significantly increased fat excretion in feces.In conclusion, this dietary supplementation improved lipoprotein profile and enhanced fat excretion in feces in overweight and obese subjects.     

Sea tangle supplementation lowers blood glucose and supports antioxidant systems in streptozotocin-induced diabetic rats

Diabetes mellitus is a chronic disease associated with serious complications that may be linked to increased lipid peroxidation. This study investigated the effects of dietary supplementation of sea tangle on lipid peroxidation and antioxidant systems in streptozotocin (STZ)-induced diabetes. Forty Sprague-Dawley rats were divided into four groups (n = 10 each) fed AIN76-based diets with either sea tangle powder, water extract of sea tangle, or sodium alginate, or a control diet with no supplement. On day 21 after beginning the diets, rats received intramuscular injections of STZ (45 mg/kg of body weight) to induce diabetes. Experimental diet feeding was continued for 3 more weeks. Dietary supplementation with water extract of sea tangle resulted in lower plasma glucose compared with the control and sodium alginate groups. There was no significant difference in plasma and hepatic lipid peroxides among the groups. Sea tangle and sodium alginate did not affect activities of catalase and glutathione peroxidase; however, supplementation of water extract of sea tangle resulted in higher superoxide dismutase activity as compared with the control and sodium alginate groups. The plasma concentration of alpha-tocopherol increased in the sea tangle water extract group, but the hepatic concentration of alpha-tocopherol was not affected by dietary supplementation. Plasma retinol was not different among experimental groups. In conclusion, our results showed that water extract of sea tangle reduces plasma glucose and protects the antioxidant system in diabetic rats. These results suggest that water extract of sea tangle contains unknown physiologically active components, other than alginic acid, that may exert a protective effect against diabetes.     

膳食实物宣教对2型糖尿病患者营养知识认知水平和血糖的影响

目的了解糖尿病患者的营养知识水平,探索适合糖尿病患者的营养宣教方式。方法采用整群随机抽样方法抽取郑州市两所医院256名住院2型糖尿病患者,随机分为试验组与对照组。对照组采用传统的营养宣教模式,试验组在传统的营养宣教法的基础上给予膳食实物宣教,采用t检验、x^2检验对两组患者的营养知识认知情况和血糖水平进行比较与评价。结果两组患者在营养宣教干预前的认知水平的差异无统计学意义,两组患者经宣教干预后营养知识认知水平均有一定的提高,其中膳食实物宣教组患者的平均认知得分为（86．5±3．8）,显著高于对照组（71．5±4．6）,差异有统计学意义（￡=9．089,P〈0．05）;两组患者干预后的餐后2h血糖均明显下降,其中膳食实物宣教组餐后2h血糖（9．15±1．06）mmol／L,与对照组（11．32±0．84）mmol／L之间的差异有统计学意义（t=6．273,P〈0．05）。结论膳食实物宣教可提高糖尿病患者的营养知识,改善膳食理念,有助于2型糖尿病患者控制餐后血糖,较传统营养宣教方式更直接、依从性更好。     

Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients

OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.     

罗汉参对糖尿病小鼠降糖作用的研究

目的观察罗汉参对糖尿病模型小鼠的降糖作用。方法选用昆明种雄性小白鼠(28～32g)124只,对100只小鼠连续2天采用腹腔注射四氧嘧啶(200mg/kg),注射后自由进食。5天后测小鼠空腹血糖值大于10.0mmol/L小于25mmol/L为糖尿病模型小鼠。模型小鼠按照空腹血糖值随机分为4组:模型对照组和低、中、高剂量组,每组12只,分别给予基础饲料和含有5%、10%和20%罗汉参的饲料喂养。24只正常小鼠按空腹血糖值随机分为空白对照组和阳性对照组,每组12只,分别给予基础饲料和含有20%罗汉参的饲料喂养,6周后进行血糖和葡萄糖耐量实验。结果高剂量组小鼠的空腹血糖值较实验前明显降低(P<0.05),与模型对照组相比也明显降低(P<0.05)。高剂量组在0、0.5、2h的血糖值及血糖曲线下面积都明显低于模型对照组和低剂量组。中剂量组只在0.5h的血糖值明显低于模型对照组。其余各组指标的差异无显著性。结论罗汉参具有降低糖尿病小鼠血糖和改善糖耐量的功效。     

Dietary glutamine supplementation reduces plasma nitrate levels in rats

It was recently shown that L-glutamine inhibits vascular nitric oxide (NO) production in vitro. The present study investigated the effect of glutamine enriched enteral diets on in vivo NO production in the rat. Nitrate, the stable end-product of NO production, was measured in plasma and 24 h urine collections in glutamine supplemented rats (6.25%, 12.5% and 25% w/w) and compared to the effect of isocaloric, nitrogenous control diets. Glutamine supplementation increased plasma levels of glutamine (up to 91%), arginine (up to 17%) and citrulline (up to 54%). After 1 week of glutamine supplementation plasma nitrate levels were significantly reduced by 50% compared to control (P < 0. 0001); irrespective of the amount of supplementation. No further decrease was observed after 2 weeks of feeding. No differences in daily urinary losses were found between the groups. These results point to an in vivo inhibitory effect of glutamine supplemented enteral feeding on NO production.     

Dietary diacylglycerol-rich oil stimulation of glucose intolerance in genetically obese rats

The effects of dietary 1,3-diacylglycerol-rich oil (DG oil) on glucose and lipid metabolism were investigated in comparison with triacylglycerol (TG) oil in female genetically obese Wistar fatty rats. The obese rats and their lean littermates (8 wk old) were fed a synthetic diet containing 10%, (w/w) DG or TG oil for 5 wk. The body weights, abdominal fat weights, and the plasma and liver TG concentrations were not significantly different due to dietary fat type in the obese and lean rats. The plasma glucose concentrations were significantly elevated by dietary DG oil as compared to TG oil in the portal vein and inferior vena cava of obese and lean rats. The plasma free fatty acid concentrations were markedly elevated by dietary DG oil as compared to TG oil in the portal vein and inferior vena cava of both genotype rats, particularly in the obese rats. In the glucose tolerance test, the obese rats fed DG oil showed glucose intolerance, possibly due to the markedly elevated plasma free fatty acids. Thus, the effects of dietary DG oil on lipid-lowering effects and anti-obesity were not observed in either genotype in the present study. Moreover, it is remarkable that glucose intolerance was induced by dietary DG oil in the genetically obese rats. dietary     

老年糖尿病合并急性脑梗死血糖水平与神经功能缺损及预后相关性分析

目的　探讨老年糖尿病患者合并脑梗死时血糖水平与神经功能缺损及预后的关系。方法　对1 0 0例老年糖尿病合并脑梗死患者进行回顾性分析,按神经功能缺损程度分为轻、中、重三组,按入院时血糖水平分为A、B、C三组,对其进行分析,与同期住院的非糖尿病急性脑梗死患者1 0 0例神经功能缺损程度进行入院时及3周后对照。结果　老年糖尿病合并脑梗死患者病灶以多发脑梗死以及椎-基底动脉系统梗死为主;就诊时血糖水平越高,神经功能缺损越重,预后越差,病死率越高(P <0 .0 1 )。结论　血糖水平的高低可作为判断病情及预后的重要参数。     

Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats

This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.     

黄精多糖预防给药对四氧嘧啶糖尿病小鼠的实验研究

目的：研究预防性给予黄精多糖（PSP）对小鼠血糖的影响和PSP对四氧嘧啶（ALx）糖尿病模型小鼠糖代谢的影响。并探讨其降糖作用及其可能的作用机制。方法：预防性给予PSP（330mg、660mg、1320nag．kg^-1,igx7d）,第8dipALx（220mg．kg^-1）,72h后,眼内眦静脉取血,葡萄糖氧化酶法测空腹血糖（FBG）,化学比色法测血清NO、NOS：实验结束时取肝脏和肾脏,制成10％匀浆,测定其NO和NOS水平;胰腺组织HE染色,观察胰腺组织病理形态变化。结果：PsP高剂量组可预防ALx对小鼠胰腺的损伤,减轻血糖急性升高,但PSP中、低剂量组对AD（引起的高血糖没有显著性影响;PSP中、高剂量能够降低ALX糖尿病小鼠血清中升高的NO及NOS含量,但对肝脏和肾脏的NO及NOS含量没有显著性影响。结论：PSP对正常小鼠的血糖没有明显影响,但可防治由ALX引起的小鼠血糖升高。对ALX诱导的糖尿病小鼠具有一定的保护作用,其机制可能与其保护胰岛,促进胰岛素分泌,降低NO和NOS水平有关。     

改善糖尿病患者血糖水平及用药依从性方法的临床研究

目的：研究家庭护理干预对改善糖尿病患者血糖水平及用药依从性的影响。方法：选择糖尿病患者400例,随机分为给予家庭护理干预的观察组和常规护理的对照组,了解患者一般情况并进行影响因素的单因素分析和多因素分析,并根据分析结果给予家庭护理干预措施,观察干预后的服药依从性及血糖水平。结果：依从性状况与文化程度、医疗费用、医患关系、对疾病及药物知识的了解程度及家庭收入呈正相关,与体育活动减少呈负相关;观察组的空腹血糖（FBG）、餐后2 h血糖（PBG）、糖化血红蛋白（HbA1c）水平均明显低于对照组,用药依从性好的例数多于对照组。结论：家庭护理干预能够有效改善糖尿病患者的用药依从性和血糖水平,具有积极的临床价值。     

Dietary manipulations influence sucrose acceptance in diet induced obese mice

The current studies examined the influence of a high fat diet on sucrose acceptance in diet induced obese (DIO) mice. C57BL/6J mice were placed on either a 45 kcal% fat diet (group DIO), or a control 10% kcal fat diet (group control) for 12 weeks followed by sucrose consumption tests and dietary manipulations. After 12 weeks exposure, body weights of DIO mice significantly exceeded those of the control mice. During subsequent sucrose consumption tests, DIO mice showed suppression in the total number of licks relative to controls. In a second experiment, consumption tests with water and a variety of sucrose concentrations revealed a hypophagic phenotype in naïve DIO mice. Licking microstructure analyses were conducted on the licking behavior of all mice, which revealed a reduction in burst size and number for DIO mice. Subsequently, we examined whether 10 days exposure to regular lab chow would alter sucrose consumption and taste evaluation in DIO mice. As a result of this dietary switch, all mice showed comparable licking behavior suggesting that exposure to the high-fat diet and diet-induced obesity may reduce preferences for other tastants in C57BL/6J mice.     

Dietary supplementation with high-selenium soy protein reduces pulmonary metastasis of melanoma cells in mice

The effect of high-selenium (Se) soy protein on pulmonary metastasis of murine B16BL6 melanoma cells was investigated in male C57BL6 mice. Isolated soy proteins (ISP) from soybeans grown with and without Se foliar application during seed development were compared. Five diets were studied, a basal AIN-93G diet or a basal diet containing 10% low-Se ISP, 5% low-Se + 5% high-Se ISP, 10% high-Se ISP, or 10% low-Se ISP supplemented with Se equivalent to that of the 10% high-Se ISP diet. The Se concentrations of the 5 diets were 0.13, 0.13, 1.9, 3.6, and 3.0 microg/g, respectively. Mice were fed the diet for 2 wk before and 2 wk after an i.v. injection of 5 x 10(4) viable cells. At necropsy, the number and size of tumors that had developed in the lungs were determined. In the control group, 13/18 mice exhibited > or = 50 tumors. The numbers of mice with > or = 50 tumors were 8/18, 7/18, 3/18, and 6/17 in the ISP-fed groups, respectively. The differences between the 10% high-Se ISP group, the Se-supplemented 10% low-Se group, and the control were significant (P < 0.05). Dietary supplementation with 10% low-Se ISP significantly decreased the mean number of tumors per group and the tumor size compared with the control. A greater reduction in these variables occurred in mice fed the 10% high-Se ISP diet. The inhibition by the Se-supplemented 10% low-Se ISP diet was similar to that by the 10% high-Se ISP diet. The whole-blood Se concentration was inversely related to the tumor number (R = -0.87, P = 0.052), tumor cross-sectional area (R = -0.91, P < 0.05), and tumor volume (R = -0.93, P < 0.05). These findings suggest that Se is responsible for the greater antimetastatic effect of the high-Se ISP. We conclude that the high-Se soy protein has a greater inhibitory effect than the low-Se soy protein on pulmonary metastasis of melanoma cells in mice.