玉米须水提物对2型糖尿病大鼠糖-脂代谢及氧化应激的影响

目的探讨玉米须水提物对2型糖尿病大鼠糖-脂代谢及氧化应激状态的影响。方法将雄性Sprague-Dawley大鼠随机分为正常对照组、模型对照组、阳性对照组(二甲双胍)及玉米须水提物低、中、高剂量组,除正常对照组外,其余各组采用高脂高糖饲养加小剂量链脲佐菌素(STZ)诱导2型糖尿病大鼠模型。各组大鼠给药干预8周后,采用全自动生化仪检测空腹血糖(FBG)、三酰甘油(TG)、血总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的水平;紫外可见分光光度计测定血清游离脂肪酸(FFA)、丙二醛(MDA)和超氧化物歧化酶(SOD)的水平。结果玉米须水提物干预后,其中中、高剂量组可显著降低大鼠血清FBG、FFA、TG和TC的水平(P<0.05或P<0.01),且呈剂量依赖型,高剂量组显著降低血清LDL-C的水平(P<0.05);同时,玉米须水提物各剂量组可显著降低大鼠血清MDA的含量,明显升高血清SOD的活性(P<0.05或P<0.01)。结论玉米须水提物可改善糖尿病大鼠糖-脂代谢,抑制氧化应激反应,对2型糖尿病大鼠产生保护作用。

成纤维细胞生长因子21调控小鼠肝脏和脂肪细胞的糖脂代谢

目的探讨成纤维细胞生长因21（FGF-21）对小鼠肝脏和脂肪细胞糖脂代谢及重要转录因子的影响。方法分别构建FGF-21过表达及表达缺陷的小鼠肝细胞和脂肪细胞模型，测定各组细胞葡萄糖转运率、甘油三酯含量以及重要转录因子的表达改变。结果FGF-21过表达的肝脏和脂肪细胞内FGF-21表达均显著增加（4．8倍和4．2倍，P〈0．05），而表达缺陷的各组细胞FGF-21分别降低约86．3％和77．8％（P〈0．05）。过表达FGF-21的脂肪细胞葡萄糖转运率升高约74％，甘油三酯降低约45％，细胞内葡萄糖转运子1、胰岛素受体底物1、PPARγ、脂肪甘油三酯脂肪酶（ATGL）、激素敏感性脂肪酶（HSL）和脂肪细胞脂肪酸结合蛋白2（ap2）增加（均P〈0．05）；而表达缺陷时葡萄糖转运率降低约31．2％，甘油三酯升高约36．9％，除胰岛素受体底物1外其余转录因子表达均降低（均P〈0．05）。FGF-21对肝细胞葡萄糖转运率无显著影响（P〉0．05）。而FGF-21过表达的肝细胞内PPARγ、羟甲基戊二酸单酰辅酶A还原酶（HMGR）、磷酸烯醇式丙酮酸羧激酶（PEPCK）降低，低密度脂蛋白受体表达升高；表达缺陷时则相反（P〈0．05）。结论FGF-21可能通过影响脂肪细胞葡萄糖摄取和肝细胞糖异生从而调节糖代谢平衡；而且FGF-21可能在脂肪细胞脂质代谢和肝脏胆固醇代谢中具有重要作用。

Effects of over-expressing resistin on glucose and lipid metabolism in mice

Resistin,a newly discovered peptide hormone mainly secreted by adipose tissues,is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However,some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans,no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study,we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection,serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice,both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control,whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore,lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.

Effect of berberine on glucolipid metabolization in diabetic skeletal muscle and its mechanism

Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.

Effect of Milrinone Induced Insulin Resistance on Glucose and Lipid Metabolism in Rats

Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible effects of milrinone on glucose metabolism andinsulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administeredvarious doses of milrinone (1, 5, 25μmoL·kg^(-1)) and were compared with controls. Ahyperinsulinaemic-eugly-caemic clamp was established in counscious rats, andmilrinone(25μmoL·kg^(-1)) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 minduring hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gaschromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinonegroups significantly increased, compared with the controls and before dosing. The percentages ofelevation of FFA by the different milrinone doses were very similar, 50%, and 52% , 55% for 1, 5,and 25 μmoL·kg^(-1), repectively, at 2 min after dosing. Plasma insulin levels were significantlyelevated in the 5 and 25 μmoL·kg^(-1) groups, and the effect of milrione on glucose concentrationwas detectable only in 25μmoL·kg^(-1) group. During hyperinsulinaemic clamping, there weresignificant increase, in plasma FFA (from 173 +- 15 to 634 +- 87μmoL·kg^(-1)) and hepatic glucoseproduction (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and aslight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires theability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization inperipheral tissue. Therefore, milrinone administration may induce an acute insulin resistance invivo.

Endocrine and paracrine role of bile acids

Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glucose metabolism and modulate temperature and energy homeostasis. Furthermore, bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death. Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracefular kinases and of the plasma membranebound, G-protein coupled bile acid receptor TGRS/Gpbar-1.

Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease

The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD.

Way back for fructose and liver metabolism:Bench side to molecular insights

The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease(NAFLD),dyslipidemia(mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.

Should nonalcoholic fatty liver disease be regarded as a hepatic illness only?

The highly increasing prevalence of obesity and type 2 diabetes mellitus in the general population makes nonalcoholic fatty liver disease the most common diagnosis in every-day practices. Lifestyle changes （mainly exercise withdrawal and weight gain） have probably heightened the prevalence of nonalcoholic fatty liver disease. Mortality in patients with Nonalcoholic Fatty Liver Disease is significantly higher when compared with that of the same age-gender general population. Hepatologists claim to bear a new burden, being Nonalcoholic Fatty Liver Disease strongly linked to systemic diseases.

Role of vanadyl acetylacetonate-induced elevation of reactive oxygen species in the regulation of lipolysis and glucose metabolism in 3T3L1 adipocytes

In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.

Observation of the efficacy and safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation for patients with prediabetes

Objective:To observe the safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation in treating patients with prediabetes and its effects on blood glucose and lipid metabolism.Methods:One hundred and two patients with prediabetes were divided into a manipulation group and a control group according to the random number table method,with 51 cases in each group.All patients received the general behavioral intervention for prediabetes,with additional Song-Relaxing and Zhen-Vibrating abdomen manipulation in the manipulation group and oral metformin hydrochloride tablets in the control group.Both groups received the intervention for six months.Results:Fourteen patients dropped out during the treatment,and a total of 88 patients completed the trial,including 45 cases in the manipulation group and 43 cases in the control group.After the treatment,the prediabetes control rate was 93.3%in the manipulation group and 74.4%in the control group,and the difference between the two groups was statistically significant(P<0.05);no patient in the manipulation group progressed to diabetes,while the rate of conversion to diabetes in the control group was 6.9%,with a significant difference between the two groups(P<0.05).After the treatment,the body mass index(BMI),glycosylated hemoglobin A1c(HbA1c),fasting plasma glucose(FPG),2-hour postload plasma glucose(2hPG)level during an oral glucose tolerance test(OGTT),fasting insulin(FINS),homeostasis model assessment-2 of insulin resistance(HOMA2-IR),total cholesterol(TC),and triglycerides(TG)decreased in both groups versus baseline,with significant differences within the groups;the levels of all indicators were lower in the manipulation group than in the control group(P<0.05),and the differences between the two groups were more prominent at the sixth month(P<0.01).At the sixth month,the high-density lipoprotein cholesterol(HDL-C)in the manipulation group was increased,while there was no significant change in the control group.In the control group,three patients reported mild gastrointestinal reactions at the initial dosing,which improved after medication adjustment.No other adverse events were observed in either group.Conclusion:Both metformin hydrochloride tablets and the Song-Relaxing and Zhen-Vibrating abdomen manipulation can improve blood glucose and lipid metabolism and reduce insulin resistance and clinical discomfort in patients with prediabetes,but the Song-Relaxing and Zhen-Vibrating abdomen manipulation has higher efficacy and safety.

Effects of Danqidihuang Granules on glucolipid metabolism in insulin-resistant rats

OBJECTIVE： To explore whether the insulin resis- tance （IR） model could be established through feed- ing Sprague-Dawley （SD） rats high-sugar and high-fat diets and to further observe the preven- tive and treatment effects of different doses of Dan- qidihuang Granules in rats. METHODS： Thirty-two SD rats were divided ran- domly into control group A （given regular feed）, model group B （food high in sugar and fat）, inter- vention group C （food high in sugar and fat as well as regular doses of Danqidihuang Granules）, and in- tervention group D （food high in sugar and fat as well as double doses of Danqidihuang Granules）. The interventions were for 8 weeks. Motion, change in color, body weight, and food intake, as well as plasma lipids （including low-density lipopro- tein-cholesterol （LDL-C）, high-density lipopro- tein-cholesterol （HDL-C）, total cholesterol （TC） and triglyceride （TG）, fasting blood glucose （FBG）, fast-ing insulin （FINs） levels, insulin sensitivity index （ISI）, and insulin resistance index （HOMO-IR） were observed. RESULTS： At the end of the second week of the ex- periment, the appetite and activities of rats in groups B, C and D decreased significantly com- pared with group A. The fur of the rats in those three groups was curly. After the fourth week, the activities, food intake and color of rats in group B were worse than those in groups C and D, but there were no significant differences in weight （P〉0.05）. Compared with group A, LDL-C, TC, FBG and HO- MO-IR in model group 13 were increased significant- ly （P〈0.05）, whereas the FINs and ISI increased obvi- ously （P〈0.05）. The levels of LDL-C and TC in group D was decreased obviously compared with those in group C, and HOMO-IR in group D was less than that in group B CP〈0.05）. CONCLUSION： Danqidihuang Granules helped to prevent and improved the insulin resistance of rats.

Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy

Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.