Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice

This study examines whether anti-diabetic effects of genistein and daidzein are mediated by hepatic glucose and lipid regulating enzyme activities in type 2 diabetic animals. Male C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The blood glucose and HbA(1c) levels were significantly lower in the genistein and daidzein groups than in the control group, while glucose tolerance only was significantly improved in the genistein-supplemented group. The plasma insulin and C-peptide levels did not differ significantly between groups, yet the glucagon level was lower in the genistein and daidzein groups compared to that in the control db/db or db/+ group. The genistein and daidzein supplements increased the insulin/glucagon ratio in the type 2 diabetic animals. While the hepatic glucokinase activity was significantly lower in the db/db control group, the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly higher in the control group compared to the db/+ group. Interestingly, these hepatic glucose metabolizing enzyme activities were reversed by the genistein and daidzein supplementation in db/db mice compared to the control group. The hepatic fatty acid synthase, beta-oxidation and carnitine palmitoyltransferase activities were all significantly lower in the genistein and daidzein groups than in the control group. The genistein and daidzein supplements also improved the plasma total cholesterol, triglyceride, HDL-cholesterol/total cholesterol, free fatty acid and hepatic triglyceride concentrations in the db/db mice. These results suggest that genistein and daidzein exert anti-diabetic effect in type 2 diabetic conditions by enhancing the glucose and lipid metabolism.     

Aberrations in the diurnal rhythms of plasma glucose, plasma insulin, liver glycogen, and hepatic glycogen synthase and phosphorylase activities in genetically diabetic (db/db) mice

The diurnal rhythms of plasma glucose, insulin, liver glycogen, and hepatic glycogen synthase and phosphorylase activities were determined in control and genetically diabetic (db/db) mice 8 weeks of age. The diabetic mice showed wide fluctuations in their plasma glucose levels, although being similar to controls near the end of the light period. Little variation was observed in their elevated plasma insulin levels. Liver glycogen levels in diabetic mice were not depleted to the low levels seen in controls during the last part of the light period but were maintained at significantly higher levels. However, maximum attained glycogen levels were similar in the two groups of mice. Alterations were also observed for the diurnal rhythms of glycogen synthase and phosphorylase activities, although again the daily maximums were similar in control and diabetic mice. These findings suggest that the reported changes of several of these metabolic parameters in the db/db mouse may be due to alterations in the diurnal pattern rather than to absolute changes.     

SGK1 抑制剂改善糖代谢紊乱的作用研究

目的:观察血清和糖皮质激素诱导的蛋白激酶1(serum and glucocorticoid-induced protein kinase1,SGK1)抑制剂对db/db小鼠糖代谢紊乱的改善作用,初步探讨该作用是否与改善脂肪组织功能紊乱有关。方法:将db/db小鼠随机分为db/db组、抑制剂组,同时设db/m组,db/db组、db/m组小鼠给予普通饲料喂养,抑制剂组小鼠给予含SGK1抑制剂的饲料喂养,干预8周。观察体重、摄食量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,Hb A1C),干预8周后行腹腔葡萄糖耐量试验(intraperitoneal glucose tolerance test,IPGTT)、腹腔胰岛素耐量试验(intraperitoneal insulin tolerance test,IPITT)。酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测血清空腹胰岛素(fasting insulin,FINS)水平,计算胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)及胰岛素敏感性指数(insulin sensitivity index,ISI)。实时定量荧光PCR(real-time PCR)法检测脂肪组织中SGK1、脂肪细胞因子m RNA表达水平。结果:干预8周后,抑制剂组体重、FBG、Hb A1C、IPGTT、IPITT均低于db/db组(P0.05),摄食量无明显差异。与db/db组相比,抑制剂组血清FINS有下降趋势,HOMA-IR明显降低,ISI明显升高(P0.05)。SGK1抑制剂干预治疗后,脂肪组织中SGK1、单核细胞趋化因子-1(monocyte chemotactic protein-1,MCP-1)、凝血酶元激活因子的抑制因子-1(plasminogen activator inhibitor 1,PAI-1)m RNA表达下降(P0.05),脂联素(adiponectin)m RNA表达无明显变化。结论:SGK1抑制剂干预治疗可一定程度改善db/db小鼠糖代谢紊乱,该作用可能部分与改善脂肪组织功能紊乱有关。     

Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats

In the current study, the effect of soy protein and genistein, one of the main isoflavones in soybeans, on blood glucose, lipid profile, and antioxidant enzyme activities in streptozotocin (STZ)-induced diabetic rats was investigated. Male Sprague-Dawley rats were divided into nondiabetic control, STZ, STZ-genistein supplemented group (STZ-G; 600 mg/kg diet), and STZ-isolated soy protein supplemented group (STZ-ISP; 200 g/kg diet). Diabetes was induced by a single injection of STZ (50 mg/kg BW) freshly dissolved in 0.1 mol/L citrate buffer (pH 4.5) into the intraperitonium. Diabetes was confirmed by measuring the fasting blood glucose concentration 48-h post-injection. The rats with blood glucose level above 350 mg/dL were considered to be diabetic. Genistein and ISP were supplemented in the diet for 3 weeks. The supplementation of genistein and ISP increased the plasma insulin level but decreased the HbA(IC) level of the STZ-induced diabetic rats. The supplementation of genistein and ISP increased the glucokinase level of the STZ-induced diabetic rats. A significant reduction in glucose-6-phosphatase was observed in the groups treated with genistein and ISP in comparison with the diabetic control group. Hepatic superoxide dismutase, catalase, and glutathione peroxidase activities of the STZ-induced diabetic rats were significantly decreased in comparison with the control rats. Administering genistein and ISP to the STZ-induced diabetic rats significantly increased those enzyme activities. The concentration of thiobarbituric acid reactive substances in the STZ-induced diabetic rats was significantly elevated, while the genistein and ISP supplement decreased it to the control concentration. Genistein and ISP supplements seem to be beneficial for correcting the hyperglycemia and preventing diabetic complications.     

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

Effect of chronic supplementation with branched-chain amino acids on the performance and hepatic and muscle glycogen content in trained rats

The objective of this study was to evaluate the effects of a diet supplemented with branched-chain amino acids (BCAA; 3.57% and 4.76%) on the performance and glycogen metabolism of trained rats. Thirty-six adult male Wistar rats received the control diet (AIN-93M) (n=12) and two diets supplemented with BCAA (S1: AIN-93M+3.57% BCAA, n=12, and S2: AIN-93M+4.76% BCAA, n=12) for 6 weeks. The training protocol consisted of bouts of swimming exercise (60 min day(-1)) for 6 weeks at intensities close to the lactate threshold. On the last day of the experiment, all groups were trained for 1 h (1H) or were submitted to the exhaustion test (EX). The time to exhaustion did not differ between groups. The groups submitted to the exhaustion test presented a reduction in plasma glucose and an increase in plasma ammonia and blood lactate concentrations compared to the 1H condition. In the 1H condition, hepatic glycogen concentration was significantly higher in group S2 compared to the control diet and S1 groups (132% and 44%, respectively). Group S2 in the 1H condition presented a higher muscle glycogen concentration (45%) compared to the control diet group. In the EX condition, a significantly higher hepatic glycogen concentration was observed for group S2 compared to the control diet and S1 groups (262% and 222%, respectively). Chronic supplementation with BCAA promoted a higher hepatic and muscle glycogen concentration in trained animals, with this effect being dose dependent.     

Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition

The purpose of the current study was to evaluate the lipid lowering and antioxidant capacity of naringin in LDL receptor knockout (LDLR-KO) mice fed a cholesterol (0.1 g/100 g) diet. As such, naringin or lovastatin (0.02 g/100 g) was supplemented in a cholesterol diet for 6 weeks. The naringin and lovastatin supplementation significantly lowered the plasma total cholesterol level compared to the control group. The plasma and hepatic triglyceride level was only lowered by the lovastatin supplement, while the hepatic cholesterol content was lowered by both the naringin and lovastatin supplements compared to the control group. The hepatic HMG-CoA reductase activity was significantly lower in the naringin and lovastatin supplemented groups than in the control group, whereas the ACAT activity was unaffected. The excretion of total sterol was significantly higher in the naringin and lovastatin groups compared to the control group due to significant changes in the acidic and neutral sterol, respectively. When comparing the hepatic antioxidant enzyme activities, the superoxide dismutase, catalase, and glutathione reductase activities were all significantly higher in the naringin-supplemented group than in the control group, while only the lovastatin supplement increased the glutathione reductase activity. Accordingly, the current results confirmed that naringin lowers the plasma cholesterol level via the inhibition of hepatic HMG-CoA reductase activity and increases the excretion of fecal sterol. Naringin was also found to improve the activities of hepatic antioxidant enzymes against oxidative stress in a hypercholesterolemic animal model, i.e. cholesterol-fed LDLR-KO mice.     

Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle.

The purpose of this study was to investigate the role of insulin on skeletal muscle GLUT-4 protein expression and glycogen storage after postexercise carbohydrate supplementation. Male Sprague-Dawley rats were randomly assigned to one of six treatment groups: sedentary control (Con), Con with streptozocin (Stz/C), immediately postexercise (Ex0), Ex0 with Stz (Stz/Ex0), 5-h postexercise (Ex5), and Ex5 with Stz (Stz/Ex5). Rats were exercised by swimming (2 bouts of 3 h) and carbohydrate supplemented immediately after each exercise session by glucose intubation (1 ml of a 50% wt/vol). Stz was administered 72-h before exercise, which resulted in hyperglycemia and elimination of the insulin response to the carbohydrate supplement. GLUT-4 protein of Ex0 rats was 30% above Con in fast-twitch (FT) red and 21% above Con in FT white muscle. In Ex5, GLUT-4 protein was 52% above Con in FT red and 47% above Con in FT white muscle. Muscle glycogen in FT red and white muscle was also increased above Con in Ex5 rats. Neither GLUT-4 protein nor muscle glycogen was increased above Con in Stz/Ex0 or Stz/Ex5 rats. GLUT-4 mRNA in FT red muscle of Ex0 rats was 61% above Con but only 33% above Con in Ex5 rats. GLUT-4 mRNA in FT red muscle of Stz/C and Stz/Ex0 rats was similar but significantly elevated in Ex5/Stz rats. These results suggest that insulin is essential for the increase in GLUT-4 protein expression following postexercise carbohydrate supplementation.     

Glucose metabolism in perfused mouse hearts overexpressing human GLUT-4 glucose transporter

Glucose and fatty acid metabolism was assessed in isolated working hearts from control C57BL/KsJ-m+/+db mice and transgenic mice overexpressing the human GLUT-4 glucose transporter (db/+-hGLUT-4). Heart rate, coronary flow, cardiac output, and cardiac power did not differ between control hearts and hearts overexpressing GLUT-4. Hearts overexpressing GLUT-4 had significantly higher rates of glucose uptake and glycolysis and higher levels of glycogen after perfusion than control hearts, but rates of glucose and palmitate oxidation were not different. Insulin (1 mU/ml) significantly increased glycogen levels in both groups. Insulin increased glycolysis in control hearts but not in GLUT-4 hearts, whereas glucose oxidation was increased by insulin in both groups. Therefore, GLUT-4 overexpression increases glycolysis, but not glucose oxidation, in the heart. Although control hearts responded to insulin with increased rates of glycolysis, the enhanced entry of glucose in the GLUT-4 hearts was already sufficient to maximally activate glycolysis under basal conditions such that insulin could not further stimulate the glycolytic rate.     

Dietary zinc supplementation attenuates hyperglycemia in db/db mice

Although zinc (Zn) deficiency has been associated with insulin resistance, and altered Zn metabolism (e.g., hyperzincuria, low-normal plasma Zn concentrations) may be present in diabetes, the potential effects of Zn on modulation of insulin action in Type II diabetes have not been established. The objective of this study was to compare the effects of dietary Zn deficiency and Zn supplementation on glycemic control in db/db mice. Weanling db/db mice and lean littermate controls were fed Zn-deficient (3 ppm Zn; dbZD and InZD groups), Zn-adequate control (30 ppm Zn; dbC and InC groups) or Zn-supplemented (300 ppm Zn; dbZS and InZS groups) diets for 6 weeks. Mice were assessed for Zn status, serum and urinary indices of diabetes, and gastrocnemius insulin receptor concentration and tyrosine kinase activity. Fasting serum glucose concentrations were significantly lower in the dbZS group compared with the dbZD group (19.3 +/- 2.9 and 27.9 +/- 4.1 mM, respectively), whereas the dbC mice had an intermediate value. There was a negative correlation between femur Zn and serum glucose concentrations (r = -0.59 for lean mice, P = 0.007). The dbZS group had higher pancreatic Zn and lower circulating insulin concentrations than dbZC mice. Insulin-stimulated tyrosine kinase activity in gastrocnemius muscle was higher in the db/db genotype, and insulin receptor concentration was not altered. In summary, dietary Zn supplementation attenuated hyperglycemia and hyperinsulinemia in db/db mice, suggesting that the roles of Zn in pancreatic function and peripheral tissue glucose uptake need to be further investigated.     

MRNA and enzyme activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 are elevated in C57BL/KsJ-db/db mice.

To evaluate the importance of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in insulin resistant diabetic C57BL/KsJ-db/db mice, we measured the activity and mRNA level of 11beta-HSD1 in the liver of db/db mice and their heterozygote litter mates, db/+m mice. The blood glucose, plasma insulin, and corticosterone levels of db/db mice were significantly higher than those of db/+m mice. Despite hyperinsulinemia, the activity level of this enzyme was significantly higher in db/db mice, and the mRNA level of hepatic 11beta-HSD1 was also significantly higher in db/db mice. Since hepatic 11beta-HSD1 in vivo mainly functions as 11-keto-reductase and does not work as 11beta-oxidase, these results suggest that the rate of hepatic conversion of 11-dehydrocorticosterone to corticosterone is increased in db/db mice, resulting in higher glucocorticoid activity in the liver. The increased hepatic corticosterone concentration due to the elevation of 11beta-HSD1 and high plasma corticosterone concentration may antagonize the action of insulin and cause insulin resistance. These findings have a potentially important implication for relationships between increased hepatic 11beta-HSD1 and insulin resistance in db/db mice. The present paper is the first to demonstrate the increased activities and mRNA level of hepatic 11beta-HSD1 in db/db mice.     

Hepatic glycogen metabolism in the db/db mouse

Summary Knowledge of the metabolic changes that occur in insulin-resistant type 2 diabetes is relatively lacking compared to insulin-deficient type 1 diabetes. This paper summarizes the importance of the C57BL/KsJ-db/db mouse as a model of type 2 diabetes, and illustrates the effects that insulin-deficient and insulin-resistant states have on hepatic glycogen metabolism. A longitudinal study of db/db mice of ages 2–15 weeks revealed that significant changes in certain parameters of hepatic glycogen metabolism occur during this period. The liver glycogen levels were similar between diabetic and control mice. However, glycogen particles from db/db mice were on average smaller in mass and had shorter exterior and interior chain lengths. Total phosphorylase and phosphorylase a activities were elevated in the genetically diabetic mice. This was primarily due to an increase in the amount of enzymic protein apparently the result of a decreased rate of degradation. It was not possible to find a consistent alteration in glycogen synthase activity in the db/db mice. Glycogen synthase and phosphorylase from diabetic liver revealed some changes in kinetic properties in the form of a decrease in V_max, and altered sensitivity to inhibitors like ATP. The altered glycogen structure in db/db mice may have contributed to changes in the activities and properties of glycogen synthase and phosphorylase. The exact role played by hormones (insulin and glucagon) in these changes is not clear but further studies should reveal their contributions. The db/db mouse provides a good model for type 2 diabetes and for fluctuating insulin and glucagon ratios. Its use should clarify the regulation of hepatic glycogen metabolism and other metabolic processes known to be controlled by these hormones. The other animal models of type 2 diabetes, ob/ob mouse and fatty Zucker (fa/fa) rat, show similar impairment of hepatic glycogen metabolism. The concentrations of glycogen metabolizing enzymes are high and in vitro studies indicate enhanced rate of glycogen synthesis and breakdown. However, streptozotocin-induced diabetic animals and BB rats which resemble insulin-deficient type 1 diabetes are characterized by decreased glycogen turnover as a result of reduction in the levels of glycogen metabolizing enzymes.     

The effect of 5 days of aspartate and asparagine supplementation on glucose transport activity in rat muscle

The consumption of protein supplements containing amino acids is increasing around the world. Aspartate (Asp) and asparagine (Asn) are amino acids metabolized by skeletal muscle. This metabolism involves biochemical pathways that are involved in increasing Krebs cycle activity via anaplerotic reactions, resulting in higher glutamine concentrations. A connection between amino acid supplementation, glycogen concentration, and glucose uptake has been previously demonstrated. The purpose of this study was to evaluate the effect of Asp and Asn supplementation on glucose uptake in rats using three different glycogen concentrations. The results indicate that Asp and Asn supplementation in rats with high glycogen concentrations (fed state) further increased the glycogen concentration in the muscle, and decreased in vitro 2‐deoxyglucose (a glucose analog) uptake by the muscle at maximal insulin concentrations. When animals had a medium glycogen concentration (consumed lard for 3 days), glucose uptake was higher in the supplemented group at sub‐maximal insulin concentrations. We conclude that supplementation of Asp and Asn reduced glucose transport in rat muscle only at higher levels of glycogen. The ingestion of lard for 3 days changed the responsiveness and sensitivity to insulin, and that group had higher levels of insulin sensitivity with Asp and Asn supplementation. Copyright © 2009 John Wiley & Sons, Ltd.     

高脂饮食和地塞米松联合诱导胰岛素抵抗大鼠模型

目的用高脂饲料＋地塞米松（dexamethasone,DEX）隔日腹腔注射建立实验性胰岛素抵抗大鼠模型,研究该模型糖代谢、脂代谢和激素水平等方面的变化。方法采用Wistar雄性大鼠,分为正常对照组、高脂组、DEX组（1mg/kg,i.p.）和高脂＋DEX组（1mg/kg,i.p.）,连续观察8周,每周测定大鼠空腹血糖,分别于造模第2周和第8周测糖耐量,8周后处死大鼠,测定胸腺、脾脏、肝脏等脏器重量。结果高脂饲料能加重腹腔注射DEX造成的空腹血糖升高,造模第8周空腹血糖（7.7±0.7）较空白组（6.5±0.6）显著升高。使模型动物糖耐量明显异常,肝糖原、肌糖原含量显著增加,血浆胰岛素及游离脂肪酸水平显著升高,各脏器指数明显增加。结论高脂＋DEX隔日腹腔注射能成功诱导胰岛素抵抗大鼠模型,这种造模方法较单纯注射DEX或单纯高脂饲养成模率高,造模周期短。     

Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes

Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.     

Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats

Summary. Taurine, a potent antioxidant has been reported to show an antidiabetic effect in streptozotocin-induced diabetes mellitus in which the development of hyperglycemia results from the damage to β cells of pancreas by reactive oxygen species. In addition, taurine also increases the excretion of nitrite and enhances the formation of kinins and would be expected to improve insulin resistance. The effect of taurine on insulin sensitivity was examined in the high fructose-fed rats, an animal model of insulin resistance. Male Wistar rats of body weight 170–190 g were divided into 4 groups: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented fructose-fed group. An intravenous glucose tolerance test (IVGTT) and a steady state plasma glucose level (SSPG) were performed before the sacrifice. The fructose-fed rats displayed hyperglycemia and insulin resistance and they had a greater accumulation of glycogen than did control rats. Hyperglycemia and insulin resistance were significantly lower in the taurine supplemented fructose-fed group than in the unsupplemented fructose-fed group. Urinary kallikrein activity was higher in taurine-treated animals than in the rats fed only fructose. The activity of membrane bound ATPases were significantly lower in fructose-fed rats than in the control rats and were significantly higher in the taurine supplemented group than in the fructose-fed group. Taurine effectively improves glucose metabolism in fructose-fed rats presumably via improved insulin action and glucose tolerance. Received January 5, 2001 Accepted August 21, 2001     

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM.     

Effect of herb supplement on hepatic enzyme activities in ddY mice.

Plasma glucose and lipid concentrations and hepatic enzyme activities were measured in male ddY mice supplemented with the herb, Echevaria glauca, to examine the effect of herbal treatment. In mice supplemented with the herb, plasma triglyceride (TG) and free fatty acid (FFA) concentrations decreased and hepatic glycolytic enzyme and glutathione peroxidase (GSHpx) activities increased significantly compared with those in the non-treated control mice. These increases in hepatic enzyme activities were not fully dose-dependent, however the higher dose and longer duration with herb supplement induced increases in the enzyme activities. It was found that dietary herb supplement caused an acceleration of hepatic function, judged by increased activities of glycolytic enzyme and GSHpx in ddY mice.     

Taurine Alters Respiratory Gas Exchange and Nutrient Metabolism in Type 2 Diabetic Rats

Objective: To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. Research Methods and Procedures: Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine‐supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long‐Evans Tokushima Otsuka) was used as the age‐matched normal control. Results: The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. Discussion: Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles.