The antilipolytic action of bis(alpha-furancarboxylato)oxovanadium(IV) in adipocytes

BACKGROUND: Previously, bis(alpha-furancarboxylato)oxovanadium(IV)(BFOV) exhibited potent hypoglycemic activity in diabetic animals. We evaluated the effects of BFOV on lipolysis in isolated rat adipocytes and lipid metabolism in fat-fed/streptozotocin (STZ)-induced diabetic rats, an animal model of type 2 diabetes. METHODS: Antilipolytic action of BFOV was investigated by observing free fatty acids (FFA) release in isolated rat adipocytes treated with epinephrine and forskolin. Diabetic rats were induced by high-fat feeding plus STZ injection (25 mg/kg, i.p.). The rats were randomly divided into non-diabetic, diabetic, diabetic-BFOV (0.02, 0.06 and 0.2 mmol/kg) and diabetic-vanadyl sulfate group. All substances were given intragastrically to rats for 4 weeks. The concentrations of blood glucose, serum lipid and leptin, as well as body weight and food intake were determined. RESULTS: FFA release from adipocytes treated with epinephrine was markedly inhibited by BFOV and vanadyl sulfate, with the IC(50) values of 0.30+/-0.20 and 0.46+/-0.26 mmol/l, respectively, but not by insulin. Whereas, the inhibition of vanadyl compounds on FFA release triggered by forskolin in adipocytes were not observed. BFOV dose-dependently reduced serum triglycerides and FFA concentrations when compared with untreated diabetic rats (P<0.05), while it did not influence cholesterol concentrations, similar to vanadyl sulfate. Serum leptin concentration was also decreased both in the BFOV- and vanadyl sulfate-treated diabetic group (P<0.05). Moreover, BFOV markedly reduced blood glucose concentration and food intake (P<0.05), but it did not change the body weight of diabetic rats. CONCLUSION: BFOV has an antilipolytic action in adipocytes mediated by catecholamines. This action was distinct from that of insulin and also not related to inhibiting the activity of adenylate cyclase. In vivo, BFOV could improve dyslipidemia and leptin sensitivity in fat-fed/STZ-diabetic rats.     

Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats

The purpose of this study was to investigate the effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Diosmin was administered to streptozotocin-induced (45 mg/kg b.w) diabetic rats at different doses (25, 50, 100 mg/kg b.w) for 45 days to assess its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin and carbohydrate metabolic enzymes, it was found that plasma glucose was significantly reduced in a dose-dependent manner when compared to the diabetic control. In addition, oral administration of diosmin (100 mg/kg b.w) significantly decreased glycosylated hemoglobin and increased hemoglobin and plasma insulin. The activities of the hepatic key enzymes such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased whereas, glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, protection against body weight loss of diabetic animals was also observed. These results showed that diosmin has potential antihyperglycemic activity in streptozotocin-nicotinamide-induced diabetic rats.     

Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling

Previous studies have shown that the traditional herbal complexGosha-jinki-gan (GJG) improves diabetic neuropathy and insulinresistance. The present study was undertaken to elucidate themolecular mechanisms related with the long-term effects of GJGadministration on insulin action in vivo and the early stepsof insulin signaling in skeletal muscle in streptozotocin (STZ)diabetes. Rats were randomized into five subgroups: (1) salinetreated control, (2) GJG treated control, (3) 2-unit insulin+ saline treated diabetic, (4) saline + GJG treated diabeticand (5) 2-unit insulin + GJG treated diabetic groups. Afterseven days of treatment, euglycemic clamp experiment at an insulininfusion rate of 6 mU/kg/min was performed in overnight fastedrats. Despite the 2-unit insulin treatment, the metabolic clearancerates of glucose (MCR, ml/kg/min) in diabetic rats were significantlylower compared with the controls (11.4 ± 1.0 vs 44.1± 1.5; P < 0.001), and were significantly improvedby insulin combined with GJG or GJG alone (26 ± 3.2 and24.6 ± 2.2, P < 0.01, respectively). The increasedinsulin receptor (IR)-ß protein content in skeletalmuscle of diabetic rats was not affected by insulin combinedwith GJG administration. However, the decreased insulin receptorsubstrate-1 (IRS-1) protein content was significantly improvedby treatment with GJG. Additionally, the increased tyrosinephosphorylation levels of IR-ß and IRS-1 were significantlyinhibited in insulin combined with GJG treated diabetes. Thepresent results suggest that the improvement of the impairedinsulin sensitivity in STZ-diabetic rats by administration ofGJG may be due, at least in part, to correction in the abnormalearly steps of insulin signaling in skeletal muscle.     

Efficacy of metformin in the treatment of NIDDM. Meta-analysis.

OBJECTIVE: The results differ concerning randomized controlled trials of the effects of metformin on blood glucose regulation and body weight. To get a systematic overview, a meta-analysis of the efficacy of metformin was performed by comparing metformin with placebo and sulfonylurea. RESEARCH DESIGN AND METHODS: All randomized controlled trials published since 1957 were selected by searching the Current List of Medical Literature, Cumulated Index Medicus, Medline, and Embase, Meta-analysis was performed calculating weighted mean difference (WMD) of fasting blood glucose, glycosylated hemoglobin, and body weight. RESULTS: Nine randomized controlled trials comparing metformin with placebo and ten comparing metformin with sulfonylurea were identified. The WMD between metformin and placebo after treatment for fasting blood glucose was -2.0 mmol/l (95% CI -2.4 to -1.7) and for glycosylated hemoglobin -0.9% (95% CI -1.1 to -0.7). Body weight WMD was not significant after treatment. Sulfonylurea and metformin lowered blood glucose and glycosylated hemoglobin equally, while there was a significant WMD of body weight (-2.9 kg [95% CI -4.4 to -1.1]) because of a 1.7-kg mean increase after sulfonylurea and a 1.2-kg mean decrease after metformin. CONCLUSIONS: Metformin lowers blood glucose and glycosylated hemoglobin significantly, compared with placebo. Metformin and sulfonylurea have an equal effect on fasting blood glucose and glycosylated hemoglobin, but the body weight is significantly lower after metformin compared with sulfonylurea treatment because of an increase in body weight after sulfonylurea treatment.     

The effects of dietary caloric restriction on antioxidant status and lipid peroxidation in mild and severe streptozotocin-induced diabetic rats

BACKGROUND: Dietary caloric restriction (CR) without malnutrition is effective in the control of diabetes mellitus by stabilizing glucose homeostasis and enhancing glycemic control. Mild and severe streptozotocin-induced diabetic and non-diabetic rats were subjected to caloric restriction and ad libitum feeding to evaluate their effects on oxidative stress and lipid profile in the plasma of experimental animals. METHODS: Mild and severe diabetes were induced in Male Wistar rats by intraperitoneal injection of 35 and 65 mg/kg streptozotocin respectively. The experimental animals were subjected to 40% caloric restriction and ad libitum feeding for 9 weeks. RESULTS: CR was effective in significantly reducing body weight, blood glucose, HbA IC and TG concentrations (all p < 0.001) in mild diabetic rats and non-significantly improving the plasma HDL-cholesterol concentrations. However, CR did not produce any significant effect on the antioxidant enzyme activities and MDA concentrations in all the groups nor in any of the parameters measured in non-diabetic rats except their overall weight change. There were significant (p < 0.001) decreases in body weight and non-significant fluctuating results in HbA IC and HDL-cholesterol in severe diabetic animals. CONCLUSIONS: These results demonstrate that caloric restriction is most effective in mild than in non-diabetic or severe diabetic animals.     

Total-body potassium in insulin-dependent diabetes mellitus

1. Total-body potassium and fat-free mass have been measured in 31 insulin-dependent diabetic patients and 31 age- and sex-matched normal volunteers. 2. Body mass index was significantly higher in the insulin-dependent diabetic patients (24.7 +/- 0.5 vs 23.3 +/- 0.4 kg/m2; P = 0.05). 3. Total-body potassium, uncorrected and corrected for weight and for fat-free mass, was not significantly different in the two groups (3281 +/- 141 mmol, 47.3 +/- 1.3 mmol/kg body weight, 60.9 +/- 1.0 mmol/kg fat-free mass, and 3315 +/- 143 mmol, 48.6 +/- 1.0 mmol/kg body weight, 60.4 +/- 0.8 mmol/kg fat-free mass, respectively, in diabetic patients and non-diabetic subjects). There was no relationship between blood glucose control, as assessed by glycated haemoglobin concentrations, and total-body potassium. 4. These results suggest, by contrast with previous reports, that in insulin-dependent diabetic patients, showing varying degrees of glycaemic control (glycated haemoglobin range 6.1-15.3%, mean 9.0%) that: (a) there is no significant abnormality of body potassium homoeostasis, and (b) there is no relation between total-body potassium and glycaemic control.     

应用同伴教育法指导社区糖尿病患者采用食品交换份法行饮食治疗的临床观察

目的 利用同伴教育法指导社区糖尿病患者采用食品交换份法进行饮食治疗,探索社区糖尿病饮食治疗的有效方法 .方法 用便利取样的方法 抽取91例2型糖尿病患者,按年龄性别匹配后随机分为同伴教育组45例和普通教育组46例,采用食品交换份法进行为期1年的饮食干预,应用t检验比较2组患者干预前后血糖、血脂、糖化血红蛋白、体重指数等指标的变化情况.结果干预后2组患者的血糖、血脂、糖化血红蛋白、体重指数等指标均有显著降低,但同伴教育组改善程度更加显著.干预后同伴教育组的空腹血糖、餐后2 h血糖、糖化血红蛋白、三酰甘油、低密度脂蛋白和体重指数均显著低于普通健康教育组,HDL-C高于普通健康教育组.结论 利用同伴教育法对糖尿病患者采用食品交换份法的健康教育更为有效.     

Modeling disease progression and rosiglitazone intervention in type 2 diabetic Goto-Kakizaki rats

The pharmacokinetics (PK) and pharmacodynamics (PD) of rosiglitazone were studied in type 2 diabetic (T2D) Goto-Kakizaki (GK) rats that received daily doses of 0, 5, or 10 mg/kg for 23 days followed by 60 days of washout. Blood glucose, plasma insulin, and hemoglobin A1c were determined over time. Oral glucose tolerance tests were performed before and at the end of treatment and after 20 days of washout to determine insulin sensitivity and β-cell function. Rosiglitazone effectively lowered glucose by inhibiting hepatic glucose production and enhancing insulin sensitivity. The glucose-insulin inter-regulation was characterized by a feedback model: glucose and insulin have their own production (k(in)) and elimination (k(out)) rate constants, whereas glucose stimulates insulin production (k(inI)) and insulin, in turn, promotes glucose utilization (k(outG)). Animal handling and placebo treatment affected glucose turnover with k(pl) = 0.388 kg/mg/day. The PK of rosiglitazone was fitted with a one-compartment model with first-order absorption. The effect of rosiglitazone was described as inhibition of k(inG) with I(max) = 0.296 and IC(50) = 1.97 μg/ml. Rosiglitazone also stimulated glucose utilization by improving insulin sensitivity with a linear factor S(R) = 0.0796 kg/mg. In GK rats, 23 days of treatment increased body weight but did not cause hemodilution. Weight gain was characterized with body weight input (k(s)(w)) and output (k(d)(w)), and rosiglitazone inhibited k(d)(w) with ID(50) = 96.8 mg/kg. The mechanistic PK/PD model quantitatively described the glucose-insulin system and body weights under chronic rosiglitazone treatment in T2D rats.     

Ⅱ型糖尿病神经病理性痛大鼠模型的建立

目的:建立Ⅱ型糖尿病神经病理性痛大鼠模型。方法:60只SD大鼠随机分为:A组(对照组,即普通饲料组,n=10),B组(实验组,即高脂高糖组,n=50)。A组以普通饲料喂养,8周后单次空腹腹腔注射柠檬酸缓冲液。B组高脂高糖喂养8周诱发胰岛素抵抗,继以不同剂量链脲佐菌素(streptozotocin,STZ,30 mg/kg、35 mg/kg、40 mg/kg)腹腔注射1次,于不同时间点分别测体重、血糖、胰岛素,计算胰岛素敏感性、机械缩足阈值和热缩足潜伏期的变化。结果:高脂高糖饮食8周,模型组大鼠体重明显增加,空腹胰岛素浓度升高,胰岛素敏感性下降,机械缩足阈值和热缩足潜伏期无变化,血糖未升高。注射STZ后,30 mg/kg剂量组血糖升高但不能长期维持;40 mg/kg剂量组血糖较高,死亡率高;35 mg/kg剂量组血糖中度升高且相对稳定,胰岛素浓度和胰岛素敏感性均降低,其机械缩足阈值和热缩足潜伏期均低于基础值和对照组(P<0.05)。结论:高脂高糖饲料喂养8周后联合腹腔注射STZ 35 mg/kg可以建立理想的Ⅱ型糖尿病神经病理性痛大鼠模型。     

Comparison of fixed-ratio versus variable-ratio regular and NPH semisynthetic human insulin in insulin-requiring diabetic patients

The efficacy and safety of a fixed combination of semisynthetic human insulin (Novolin) providing a 70:30 ratio of NPH to regular insulin versus a varying ratio of semisynthetic human insulin, regular and NPH (control group), were compared in adult insulin-dependent and noninsulin-dependent diabetic patients whose glycemic control had been stable on customized split-mix regimens of animal insulin. Seventy-eight patients were enrolled, of whom 72 were evaluated for efficacy of the respective regimens. Although the baseline fasting serum glucose concentrations were significantly higher in the fixed-ratio group than in the control group, mean serum glucose and glycosylated hemoglobin values throughout the 12 weeks of experimental treatment were not significantly different between groups. The mean serum glucose and glycosylated hemoglobin values in the fixed-ratio group also did not differ significantly from baseline; however, statistically significant increases were observed in the control group at weeks 4 and 8, but not at week 12. Total daily insulin dosages were comparable between the two groups, and body weight did not change significantly in either group. At the end of the study, the investigators judged 90% of the patients in the fixed-ratio group and 88% of the patients in the control group to be either improved or unchanged with respect to glycemic control. The frequency of hypoglycemic episodes and other clinical events did not change significantly from baseline in either group or differ significantly between the two groups at any time. The results of this study suggest that stable diabetic patients receiving animal insulin can safely be transferred to semisynthetic human insulin and that the majority of patients can maintain acceptable glycemic control with a fixed 70:30 ratio of NPH to regular semisynthetic human insulin.     

Effects of streptozotocin (STZ)-induced diabetes and insulin replacement on rat ventral prostate

Background

Diabetes mellitus due to insulin deficiency has adverse effect on all organ systems including reproductive organs. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in humans. The present investigation was designed to delineate the impact of STZ-induced diabetes and insulin replacement on the rat ventral prostate.

Methods

Healthy adult male rats of Wistar strain were divided into three groups: Group I: Control; Group II: STZ-diabetic (rats were treated with a single intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg body weight); Group III: Insulin replaced (after 3 days of STZ treatment, a group of adult male diabetic rats was given insulin at a dose of 3 U/100 g body weight in two equally divided doses at 08:00 and 18:00 h). All the rats were killed after 20 days of treatment and ventral prostate was removed and processed for biochemical estimations such as glucose oxidation, nuclear and cytosolic androgen and estrogen receptors, fructose, acid and alkaline phosphatases.

Results

STZ-diabetes significantly decreased the body weight. Glucose oxidation, androgen and estrogen receptor concentration were also decreased in ventral prostate, but the fructose concentration was increased. Specific activities of both acid and alkaline phosphatases were also markedly decreased due to diabetes.

Conclusion

The results of this study suggest adverse effects of STZ-induced diabetes on the biochemical profiles as well as androgen and estrogen receptors of rat ventral prostate. Amelioration of these changes (partially or completely) by insulin replacement indicates that optimal insulin is essential for maintaining functional integrity of ventral prostate.     

A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes

OBJECTIVE: To determine the efficacy of high-intensity progressive resistance training (PRT) on glycemic control in older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a 16-week randomized controlled trial in 62 Latino older adults (40 women and 22 men; mean +/- SE age 66 +/- 8 years) with type 2 diabetes randomly assigned to supervised PRT or a control group. Glycemic control, metabolic syndrome abnormalities, body composition, and muscle glycogen stores were determined before and after the intervention. RESULTS: Sixteen weeks of PRT (three times per week) resulted in reduced plasma glycosylated hemoglobin levels (from 8.7 +/- 0.3 to 7.6 +/- 0.2%), increased muscle glycogen stores (from 60.3 +/- 3.9 to 79.1 +/- 5.0 mmol glucose/kg muscle), and reduced the dose of prescribed diabetes medication in 72% of exercisers compared with the control group, P = 0.004-0.05. Control subjects showed no change in glycosylated hemoglobin, a reduction in muscle glycogen (from 61.4 +/- 7.7 to 47.2 +/- 6.7 mmol glucose/kg muscle), and a 42% increase in diabetes medications. PRT subjects versus control subjects also increased lean mass (+1.2 +/- 0.2 vs. -0.1 +/- 0.1 kg), reduced systolic blood pressure (-9.7 +/- 1.6 vs. +7.7 +/- 1.9 mmHg), and decreased trunk fat mass (-0.7 +/- 0.1 vs. +0.8 +/- 0.1 kg; P = 0.01-0.05). CONCLUSIONS: PRT as an adjunct to standard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes.     

Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus.

The mechanism(s) and site(s) of the insulin resistance were examined in nine normal-weight noninsulin-dependent diabetic (NIDD) subjects. The euglycemic insulin clamp technique (insulin concentration approximately 100 microU/ml) was employed in combination with hepatic and femoral venous catheterization and measurement of endogenous glucose production using infusion of tritiated glucose. Total body glucose metabolism in the NIDD subjects (4.37 +/- 0.45 mg/kg per min) was 38% (P less than 0.01) lower than in controls (7.04 +/- 0.63 mg/kg per min). Quantitatively, the most important site of the insulin resistance was found to be in peripheral tissues. Leg glucose uptake in the diabetic group was reduced by 45% as compared with that in controls (6.0 +/- 0.2 vs. 11.0 +/- 0.1 mg/kg leg wt per min; P less than 0.01). A strong positive correlation was observed between leg and total body glucose uptake (r = 0.70, P less than 0.001). Assuming that muscle is the primary leg tissue responsible for glucose uptake, it could be estimated that 90 and 87% of the infused glucose was disposed of by peripheral tissues in the control and NIDD subjects, respectively. Net splanchnic glucose balance during insulin stimulation was slightly more positive in the control than in the diabetic subjects (0.31 +/- 0.10 vs. 0.05 +/- 0.19 mg/kg per min; P less than 0.07). The difference (0.26 mg/kg per min) in net splanchnic glucose balance in NIDD represented only 10% of the reduction (2.67 mg/kg per min) in total body glucose uptake in the NIDD group and thus contributed very little to the insulin resistance. The results emphasize the importance of the peripheral tissues in the disposal of infused glucose and indicate that muscle is the most important site of the insulin resistance in NIDD.     

Cell size and glucose oxidation rate in adipose tissue from non-diabetic and diabetic obese human subjects.

1. The rate of oxidation of [1-14C]glucose to 14CO2 was examined in subcutaneous adipose tissue from fifteen obese non-diabetic subjects and from eleven obese maturity-onset diabetic patients. Production of 14CO2, measured in the basal state and in the presence of insulin, was significantly correlated with mean cell size in both the non-diabetic and the diabetic subjects, independent of age, relative weight and fasting plasma insulin concentration. 2. Comparison of the regressions of glucose oxidation rates on mean cell size indicated: (i) that insulin produced a significant increase in activity over the basal value in both groups, and (ii) that basal and insulin-stimulated activity were both significantly lower in diabetic than in non-diabetic adipose tissue.     

诺和锐30强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响

目的探讨诺和锐30强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响。方法对40例初诊2型糖尿病患者进行2周的诺和锐30治疗,分析治疗前后空腹血糖（FPG）及餐后2h血糖（2hPG）、糖化血红蛋白（HbAlc）、静脉葡萄糖耐量试验第一时项胰岛素及C肽分泌和胰岛素及C肽曲线下面积、胰岛素抵抗指数、胰岛素分泌指数、胰岛素敏感指数、空腹胰岛素（FINS）与FPG比值。结果诺和锐30治疗后,FPG、2hPG、HbAlc、胰岛素抵抗指数均较治疗前明显下降（P〈0．01）;窄腹及第一时项胰岛素和C肽的分泌、胰岛素及C肽曲线下面积、FINS与FPG比值、胰岛素分泌指数、胰岛素敏感指数均较治疗前明显升高（P〈0．01）。结论诺和锐30强化治疗能显著改善初诊2型糖尿病患者的血糖及胰岛功能。     

Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes.

To examine the relationship between the plasma glucose concentration (PG) and the pathways of hepatic glucose production (HGP), five groups of conscious rats were studied after a 6-h fast: (a) control rats (PG = 8.0 +/- 0.2 mM); (b) control rats (PG = 7.9 +/- 0.2 mM) with somatostatin and insulin replaced at the basal level; (c) control rats (PG = 18.1 +/- 0.2 mM) with somatostatin, insulin replaced at the basal level, and glucose infused to acutely raise plasma glucose by 10 mM; (d) control rats (PG = 18.0 +/- 0.2 mM) with somatostatin and glucose infusions to acutely reproduce the metabolic conditions of diabetic rats, i.e., hyperglycemia and moderate hypoinsulinemia; (e) diabetic rats (PG = 18.4 +/- 2.3 mM). All rats received an infusion of [3-3H]glucose and [U-14C]lactate. The ratio between hepatic [14C]UDP-glucose sp act (SA) and 2X [14C]-phosphoenolpyruvate (PEP) SA (the former reflecting glucose-6-phosphate SA) measured the portion of total glucose output derived from PEP-gluconeogenesis. In control rats, HGP was decreased by 58% in hyperglycemic compared to euglycemic conditions (4.5 +/- 0.3 vs. 10.6 +/- 0.2 mg/kg.min; P < 0.01). When evaluated under identical glycemic conditions, HGP was significantly increased in diabetic rats (18.9 +/- 1.4 vs. 6.2 +/- 0.4 mg/kg.min; P < 0.01). In control rats, hyperglycemia increased glucose cycling (by 2.5-fold) and the contribution of gluconeogenesis to HGP (91% vs. 45%), while decreasing that of glycogenolysis (9% vs. 55%). Under identical plasma glucose and insulin concentrations, glucose cycling in diabetic rats was decreased (by 21%) and the percent contribution of gluconeogenesis to HGP (73%) was similar to that of controls (84%). These data indicate that: (a) hyperglycemia causes a marked inhibition of HGP mainly through the suppression of glycogenolysis and the increase in glucokinase flux, with no apparent changes in the fluxes through gluconeogenesis and glucose-6-phosphatase; under similar hyperglycemic hypoinsulinemic conditions: (b) HGP is markedly increased in diabetic rats; however, (c) the contribution of glycogenolysis and gluconeogenesis to HGP is similar to control animals.     

Effect of angiotensin convertase inhibitors and AT1 angiotensin receptor antagonists on the development of oxidative stress in the kidney of diabetic rats.

The aim of this study was to analyse the effect of angiotensin convertase inhibitor, enalapril (ENA), and angiotensin AT-1 receptor antagonist, losartan potassium (LP), on lipid peroxidation and activities of Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase in kidneys of streptozotocin (STZ)-induced diabetic rats after 6 and 12 weeks of treatment. STZ-induced body weight changes and blood glucose concentration were not affected by either ENA or LP but both drugs significantly decreased cholesterol and triglyceride concentrations elevated in diabetic rats, inhibited kidney weight gain, and decreased albuminuria. Kidneys of STZ-diabetic rats had increased malondialdehyde content and decreased activities of antioxidant enzymes (Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase). Both ENA and LP decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats. These results confirm the role of oxidative stress in the development of diabetic nephropathy already at early stages of the development of diabetes and point to the possible antioxidative mechanism of the nephroprotective action of ENA and LP.     

甲钴胺对实验性糖尿病大鼠组织胰岛素样生长因子1基因表达及周围神经病变的影响

背景糖尿病状态造成胰岛素样生长因子1基因表达异常,后者参与糖尿病周围神经病变的发生、发展.目的探讨单剂量甲钴胺预防实验性糖尿病周围神经病变的分子学机制.设计分组对照动物实验.单位南京医科大学第一附属医院内分泌科.材料实验于2001-02/2002-01在南京医科大学动物实验中心完成.选用清洁级SD雄性大鼠80只.方法①取64只大鼠进行造模四氧嘧啶溶于生理盐水,以240 mg/kg剂量腹腔注射,48 h后,取20 mmol/L以上者为糖尿病模型.②取16只作为正常对照组,不造成糖尿病模型,仅腹腔注射等量生理盐水.③将造模成功的64只大鼠中采用猪短效和长效胰岛素按21比例每日皮下注射后根据血糖水平不同分为2组一组血糖控制较好为胰岛素治疗1组和血糖控制较差为胰岛素治疗2组,每组32只.各组取16只给予给予甲钴胺500 μg/(kg·d)肌注,分为甲钴胺+胰岛素治疗1组和甲钴胺+胰岛素治疗2组.其余每组16只用作胰岛素治疗组对照.④于实验开始时及造模成功后2周,2,3个月测定动物体质量为初质量和末质量;血糖测定用葡萄糖氧化酶法;血清果糖胺测定采用1-脱氧-1-吗咛.⑤采用VikingⅣ诱发电位仪测定诱发电位出现的波幅和感觉及运动神经传导速度.反转录聚合酶链反应法半定量分析胰岛素样生长因子1 mRNA表达.采用酶联免疫吸附分析法测定神经组织胰岛素样生长因子1肽含量.⑥组间差异采用单析因方差分析. 主要观察指标①各组大鼠各实验阶段神经组织胰岛素样生长因子1mRNA、胰岛素样生长因子1肽含量,神经电生理变化.②各组大鼠各实验阶段糖代谢指标及体质量比较.结果实验过程中糖尿病感染或急性并发症死亡3只,最终进入结果分析77只.①体质量及血糖代谢变化糖尿病成模后,甲钴胺+胰岛素治疗组分别与胰岛素治疗组血糖、果糖胺等血糖代谢指标差异不明显,体质量增长较正常对照组延缓趋势一致.②组织胰岛素样生长因子1 mRNA表达及其肽含量变化甲钴胺+胰岛素治疗组组织胰岛素样生长因子ⅠmRNA含量均不同程度高于胰岛素治疗组(P＜0.05～0.01)..糖尿病成模后2周时,坐骨神经甲钴胺+胰岛素治疗1组组织胰岛素样生长因子1mRNA含量显著高于胰岛素治疗1组(P＜0.05),与正常对照组差异不明显;甲钴胺+胰岛素治疗2组明显高于胰岛素治疗2组(P＜0.05),但低于正常对照组(P＜0.01);病程2个月时,甲钴胺+胰岛素治疗组明显低于对照组,高于相应胰岛素治疗组(P＜0.05～0.01).病程3个月时,甲钴胺+胰岛素治疗2组神经组织与胰岛素治疗2组无差异.甲钴胺对组织胰岛素样生长因子1肽含量变化的影响趋势与对胰岛素样生长因子1 mRNA基本平行.③神经电生理指标变化病程2和3个月时,甲钴胺+胰岛素治疗1组感觉和运动神经传导速度及波幅明显高于胰岛素治疗1组同期(P＜0.05);病程2个月时,甲钴胺+胰岛素治疗2组感觉神经传导速度及波幅基本明显高于胰岛素治疗2组(运动神经传导速度除外,P＜0.05).病程3个月时,甲钴胺+胰岛素治疗2组和甲钴胺+胰岛素治疗2组感觉和运动神经传导速度及波幅明显低于正常对照组(P＜0.05～0.01).结论①甲钴胺对糖尿病的血糖水平无显著影响.②甲钴胺可以通过影响实验性糖尿病大鼠组织胰岛素样生长因子1基因表达预防糖尿病外周神经病变的发生.③血糖控制较好结合甲钴胺治疗能更有效预防糖尿病外周神经病变.     

Activit�� antihyperglyc��miante d��un st��rol ��-sitoglucoside isol�� de la plante Anabasis articulata (Forssk) Moq

??-sitoglucoside saponin was separated from Anabasis articulata: plant used in traditional medicine for treatment of diabetes (Chenopodiaceae). Different methods and spectroscopic chromatography have allowed to identify the product isolated. Experiments were performed in non-diabetic mice, and in diabetic mice (glucose treated mice) showed that oral administration of the butanolic extract (saponins) 10 mg/kg decreased the glycaemia to 20.09% (P < 0.05), six hours after administration. These results also showed that oral administration of 4 mg/kg of ??-Sitoglucoside decrease the glycaemia to 24.2% (P < 0.05) after six hours of treatment and corresponding to the greatest reduction in diabetic mice (anti-hyperglycemic effect) similar to the antidiabetic action of reference molecule: glibenclamide (10 mg/kg). This dose has been able to restore the blood glucose level in diabetic mice, whereas the concentration of 2 mg/kg had no appreciable effect. This study confirms the effect of the antidiabetic compound separated.     

血糖和血脂波动对糖尿病大鼠肾脏组织氧化应激、周围神经病变以及认知功能的影响

目的分析血糖和血脂波动对糖尿病大鼠肾脏组织氧化应激、周围神经病变以及认知功能的影响。方法将无特定病原体(SPF)级雄性SD大鼠按照随机数字表法分成空白对照组(NC组)、持续高血糖组(GH组),血糖波动组(GF组)、持续高血糖血脂组(GLH组)和血糖血脂波动组(GLF组),每组各10只。经腹腔注射链脲佐菌素建立糖尿病大鼠模型,经腹腔注射葡萄糖液和胰岛素制备糖尿病血糖波动大鼠模型,经腹腔注射泰洛沙泊制备持续高血糖血脂模型,经腹腔注射葡萄糖液、泰洛沙泊、胰岛素和血脂康制备糖尿病血糖血脂波动大鼠模型,NC组注射等量0.9%氯化钠溶液。每周固定1 d检测大鼠体重,血糖、血脂波动12周后,检测大鼠血糖相关指标[最大血糖波动幅度(LAGE)、平均血糖波动幅度(MAGE)、全天血糖水平的标准差(SDBG)]、血脂相关指标[胆固醇最大波动幅度(MFC)、胆固醇平均值(MC)、胆固醇标准差(SDC)、甘油三酯最大波动幅度(MFT)、甘油三酯平均值(MT)和甘油三酯标准差(SDT)]、糖化血糖蛋白(HbA1c)、氧化应激[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)]、认知功能和坐骨神经运动传导速度(MNCV)。结果初始大鼠体重差异无统计学意义(P> 0.05)。血糖、血脂波动12周后,与NC组相比,GH组、GF组、GLH组及GLF组大鼠体重、SOD活力、GSH水平、穿越平台次数显著降低,逃避潜伏期、潜伏期距离及血糖相关指标、HbA1c、血脂相关指标、MDA水平显著升高,MNCV显著减慢,差异有统计学意义(P <0.05)。与GH组相比,GF组大鼠体重、血糖相关指标、HbA1c、血脂相关指标、SOD活力、GSH水平及穿越平台次数明显降低,MDA水平、逃避潜伏期、潜伏期距离明显升高,MNCV显著减慢,差异有统计学意义(P <0.05)。与GLH组相比,GLF组大鼠体重、血糖相关指标、HbA1c、血脂相关指标、SOD活力、GSH水平及穿越平台次数明显降低,MDA水平、逃避潜伏期、潜伏期距离明显升高,MNCV显著减慢,差异有统计学意义(P <0.05)。结论血糖、血脂波动可以使大鼠周围神经病变和认知功能障碍加重,其机制可能与氧化应激损伤增高有关。