JTT-608 restores impaired early insulin secretion in diabetic Goto-Kakizaki rats.

1. We investigated the pharmacological effects of a new antidiabetic agent, JTT-608, in comparison with the sulphonylurea tolbutamide, in Goto-Kakizaki (GK) rats, a genetic model of non-obese insulin-dependent diabetes mellitus (NIDDM). 2. In isolated perfused pancreas from GK rats, JTT-608 (200 microM) enhanced 11.1 mM glucose-stimulated insulin secretion in the first and second phases, but had little effect on insulin secretion at 2.8 mM glucose. In contrast, tolbutamide (100 microM) markedly stimulated insulin secretion at 2.8 mM glucose and enhanced the second phase of insulin secretion but not the first phase at 11.1 mM glucose. 3. In vivo JTT-608 also enhanced early insulin secretion only with glucose-loading. In contrast, tolbutamide enhanced insulin secretion both with and without glucose-loading. 4. JTT-608 (10-100 mg kg(-1)) improved oral glucose tolerance with enhanced insulin secretion in a meal tolerance test (MTT). In comparison with tolbutamide, JTT-608 improved glucose tolerance more efficiently in GK rats than in Wistar rats. 5. We conclude that in diabetic GK rats JTT-608 suppressed postprandial glucose excursions with enhanced glucose-stimulated insulin secretion, especially the first phase of insulin secretion.     

Long-term effects of glipizide on insulin secretion and blood glucose control in patients with non-insulin-dependent diabetes mellitus

Summary Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached 6.0 mmol·l^–1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of –2.8 kg by dietary control, did achieve a fasting blood glucose 6.0 mmol·l^–1 after addition of 20 mg glipizide daily. They had a sustained (2 years) increase in meal-induced insulin secretion (32% increase in postprandial C-peptide AUC), and a sustained reduction in postprandial hyperglycaemia (34% reduction in AUC). Ten of the patients took a mean daily dose <5mg (4.8 mg) and had a sustained increase in insulin secretion rate (increased C-peptide slope). The 15 patients had no elevation of basal insulin secretion and no impairment of weight reduction. The remaining 8 subjects, who showed little or no weight reduction on dietary control, had little or no reduction in fasting blood glucose despite long-term treatment with 20 mg glipizide daily, a less sustained increase in meal-induced insulin secretion, a smaller reduction of postprandial hyperglycaemia, and an increase in body weight. On diagnosis the 8 subjects did not differ from the other 15 subjects in age, body weight, blood glucose, HbA₁c, C-peptide or insulin, nor in their glucose and insulin responses to a test dose of glipizide; the main reason for the apparent drug failure appeared to be deficient compliance with dietary regulation rather than a primary inability to respond to sulphonylurea treatment. The findings indicate that glipizide is able to promote and maintain increased meal-induced insulin secretion and near-normal fasting and non-fasting blood glucose levels without continuous B cell stimulation. However, these improvements prevail mainly in subjects who persist with hypocaloric dietary regulation.     

胰岛素气雾剂经正常及糖尿病大鼠肺部给药后的降血糖作用

目的：研究胰岛素气雾剂经肺部给药后的降血糖作用。方法：建立了大鼠的肺部给药模型,通过经口有入及气管内给药两种途径将溶液型胰岛素气雾剂导入大鼠肺内,采用葡萄糖氧化酶法测定给药后正常大鼠及糖尿病大鼠的血糖水平,并计算其药理生物利用度。结果：在同一种剂量下,经口吸入和气管内给药两种途径在正常及糖尿病大鼠体内均呈现显著的降血糖作用,其药理生物利用度在正常大鼠体内分别为6．0％和11．4％,在糖尿病大鼠体内分别为5．6％和8．7％,结论：胰岛素气雾剂能有效地降低正常及糖尿病大鼠血糖,为进一步开发临床治疗糖尿病的新剂型打下基础。     

Effects of gastric bypass on blood glucose in rats with diabetes mellitus

目的 研究胃肠转流手术(GBP)对非肥胖型糖尿病大鼠的降糖效果与术后进食量、体重的关系.方法 健康雄性wistar大鼠,腹腔注射链脲佐菌素(STZ)建立糖尿病模型.随机分成3组,O组:GBP手术组;F组:饮食控制组;C组:空白对照组.观察各组大鼠体重、平均进食量,分别测定术前、术后1、2、3、4、8周空腹及灌服葡萄糖30 min后血糖水平.结果 O组GBP后4周,空腹和灌服葡萄糖后血糖分别由(20.8±4.9)、(30.2±3.1)mmol/L下降到(11.6±2.9)、(16.6±3.1)mmol/L (P＜0.01).O组体重改变无统计学意义.F组控制平均进食量约为O组的1/3并致体重显著下降,血糖下降没有O组明显.结论 胃转流术对糖尿病大鼠具有明显治疗作用,其降糖作用与术后体重下降及进食量无关.     

胃转流术对糖尿病大鼠降糖作用的实验研究

目的研究胃肠转流手术(GBP)对非肥胖型糖尿病大鼠的降糖效果与术后进食量、体重的关系。方法健康雄性wistar大鼠,腹腔注射链脲佐菌素(STZ)建立糖尿病模型。随机分成3组,O组:GBP手术组;F组:饮食控制组;C组:空白对照组。观察各组大鼠体重、平均进食量,分别测定术前、术后1、2、3、4、8周空腹及灌服葡萄糖30min后血糖水平。结果 O组GBP后4周,空腹和灌服葡萄糖后血糖分别由(20.8±4.9)、(30.2±3.1)mmol/L下降到(11.6±2.9)、(16.6±3.1)mmol/L(P<0.01)。O组体重改变无统计学意义。F组控制平均进食量约为O组的1/3并致体重显著下降,血糖下降没有O组明显。结论胃转流术对糖尿病大鼠具有明显治疗作用,其降糖作用与术后体重下降及进食量无关。     

不同剂量维生素E对糖尿病大鼠血糖的影响

目的:观察维生素E剂量与糖尿病大鼠血糖降低的关系。方法:SD大鼠分为空白对照组和实验组。实验组用链脲佐菌素制备糖尿病模型,分为无治疗组(D组),维生素E治疗1组(DE1组)(300 mg/kg),维生素E治疗2组(DE2组)(600 mg/kg),维生素E治疗3组(DE3组)(900 mg/kg)。测量各组体重、血糖和糖化血红蛋白。结果:实验组大鼠体重与空白对照组比较差异有显著性(P<0.001),但实验组各组之间比较差异无显著性(P>0.05)。实验组血糖和糖化血红蛋白均高于空白对照组(P<0.001)。在实验组之间,DE1组和D组比较差异无显著性(P>0.05),DE2组和DE3组明显低于DE1组和D组(P<0.01),同时DE3组又明显低于DE2组(P<0.05)。结论:维生素E可以有效降低糖尿病大鼠的血糖和糖化血红蛋白,同时在600～900 mg/kg范围内可能存在剂量反应关系。     

不同血糖浓度糖尿病大鼠结肠动力研究

目的探讨不同血糖水平对糖尿病大鼠结肠收缩活动的影响。方法①糖尿病模型建立,控制血糖水平分组。②活性炭推进实验,观察不同浓度血糖对结肠推进率的影响。③观察不同分组大鼠结肠纵行肌条自发收缩活动。结果①血糖、体重变化明显,P〈O．Ol。②各组结肠活动相比差异有统计学意义。结论不同血糖浓度引起结肠动力改变不同。     

葛根素增强2型糖尿病-胰岛素抵抗大鼠胰岛素敏感性和抗氧化作用

目的观察葛根素对2型糖尿病-胰岛素抵抗大鼠胰岛素敏感性及血糖、血脂和氧化应激作用。方法采用腹腔注射(ip)小剂量链脲霉素(25-30mg?kg-17d-1,qd×1d),并加饲高热量饮食(富含脂肪和蔗糖)42d,造成糖耐量减退(IGT)、IR的T2DM大鼠模型;灌胃给药(ig)葛根素0．3g?kg-1、0．15g?kg-1或二甲双胍0．25g?kg- 1,qd×28d;测病鼠空腹血糖(FBG)和口服葡萄糖耐量试验(OGTT)后2小时血糖(2hBG)以及空腹血清血糖(FSG)、三酰甘油(TG)、游离脂肪酸(FFA)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、糖化血红蛋白(GHb)、果糖胺(FRA)、丙二醛(MDA)和胰岛素(FIns)含量及超氧化物歧化酶(SOD)活性,计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(IRI)。结果葛根素和二甲双胍均能显著降低病鼠Fins和IRI,而提高ISI(P<0．01),增强胰岛素敏感性;降低FBG和OGTT。后2hBG,以及TC,LDL-C,HDL-C,TG和FFA含量(P<0．01),改善糖脂代谢紊乱;降低MDA含量和提高SOD活性(P<0．01),增强清除自由基能力。结论葛根素对T2DM大鼠能产生二甲双胍样的改善高胰岛素血症、提高胰岛素敏感性以及降糖和降血脂等效应,并具有抗氧化活性。     

丙酮酸循环回补反应与葡萄糖刺激的胰岛素分泌的关系

葡萄糖刺激的胰岛素分泌对维持机体葡萄糖代谢的稳态起着至关重要的作用。在此过程中,β细胞的线粒体一方面利用葡萄糖酵解产生的ATP引起ATP依赖的KATP通道关闭,Ca2+通道开放,Ca2+内流,促进胰岛素囊泡向胞外分泌;另一方面通过KATP通道非依赖途径,利用丙酮酸回补反应使葡萄糖充分酵解,既补充了由于糖酵解循环代谢造成的中间物的流失,又生成了促进胰岛素分泌的中间产物及促使ATP/ADP比率的增加,进一步促进胰岛素的释放。该文对丙酮酸回补反应的3个途径,即丙酮酸-苹果酸循环途径,丙酮酸-柠檬酸循环途径和丙酮酸-异柠檬酸循环途径,及其在胰岛素分泌中的作用等方面的研究进展进行了综述。     

Effect of Desmodium gangeticum extract on blood glucose in rats and on insulin secretion in vitro

Desmodium gangeticum is widely used in the indigenous system of medicine in India and is reported to contain flavone and isoflavonoid glycosides. It forms the ingredient of many Ayurvedic formulations used for diabetes. The present study was thus aimed at evaluating the insulin secretion and antidiabetic activity of Desmodium gangeticum. Treatment of diabetic rats with aerial parts of D. gangeticum extract (DG, 100 and 250 mg/kg body weight) for 3 weeks showed a significant reduction in blood glucose. D. gangeticum extract caused a significant increase in insulin secretion from MIN6 cells grown as monolayers and as pseudoislets, indicating that the antidiabetic activity may be as a result of increased insulin secretion. It also had a role on the lipid profile of the rats by causing reductions in cholesterol and triglycerides and increasing the HDL significantly (p < 0.05). This works supports the traditional use of D. gangeticum in the treatment of diabetes and this is likely to be due, at least in part, to its stimulation of insulin secretion by pancreatic islet cells.     

Effect of forskolin on islet cyclic AMP,insulin secretion,blood glucose and intravenous glucose tolerance in rats

Summary The in vivo effect of forskolin on insulin release, blood glucose and intravenous glucose tolerance test has been studied in the rat. In addition in vitro experiments on the effect of forskolin on islet cAMP and insulin release have been performed for comparison purposes.In batch incubated islets forskolin increased cAMP levels concentration dependently, the EC₅₀ being approximately 25 M. The maximal effect occurred after 5 min. In the presence of 2.8 mM glucose 10M forskolin did not stimulate insulin release; however, it potentiated both phase of 11.1 mM glucose induced insulin secretion.I. v. administration of 1.5 mg/kg of forskolin increased blood glocose levels in rats, which was associated with significant elevation of serum insulin. During an i. v. glucose tolerance test forskolin potentiated the insulin releasing capacity of glucose but did not significantly affect blood glucose levels. It is conceivable that cAMP per se does not initiate but rather amplifies insulin release by glucose. Since the synergistic effect of forskolin and glucose on insulin release in vivo is not associated with increased elimination rate it is possible that forskolin exhibits additional effects which counteract the glucose lowering action of insulin.     

The intravenous glucose tolerance test in cannulated Wistar rats: a robust method for the in vivo assessment of glucose-stimulated insulin secretion

INTRODUCTION: Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. METHODS: Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. RESULTS: Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). DISCUSSION: The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy.     

妊娠糖尿病临床血糖检验结果分析

目的:探讨饮食控制、运动及胰岛素治疗对妊娠糖尿病(GDM)患者血糖检验结果的影响。方法:用饮食控制、运动及胰岛素治疗96例妊娠糖尿病患者,统计分析其治疗前后血糖的改变。结果:严重程度完全不同GDM患者的血糖可以经饮食控制、运动及胰岛素治疗被控制在一定的浓度。结论:饮食控制、运动及胰岛素治疗都可以有效控制GDM患者血糖,血糖检测可以作为临床治疗方案选择以及预后评价的主要指标。     

Effects of propolis on blood glucose, blood lipid and free radicals in rats with diabetes mellitus.

The effects of ethanol (EEP) and water (WSD) extracts of propolis collected from north China on blood glucose, blood lipid and free radicals in rats with diabetes mellitus were studied. The results show that EEP and WSD led to decreased levels of blood glucose (FBG), fructosamine (FRU), malonaldehyde (MDA), nitric oxide (NO), nitric oxide synthetase (NOS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) in serum of fasting rats; and to increased serum levels of high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD). This suggests that propolis can control blood glucose and modulate the metabolism of glucose and blood lipid, leading to decreased outputs of lipid peroxidation and scavenge the free radicals in rats with diabetes mellitus.     

孜亚比提片对血糖和血脂作用的实验研究

目的研究孜亚比提片对2型糖尿病(T2DM)大鼠血糖和血脂的影响及机制。方法采用高脂乳剂给Wistar大鼠灌胃10d后,用毛细管法判定胰岛素抵抗性;再结合2次给药法腹腔注射四氧嘧啶,建立T2DM大鼠模型。动物分为正常对照组、模型组、孜亚比提片组(440,220 mg·kg~(-1)·d~(-1))及消渴丸组(420 mg·kg~(-1)·d~(-1))。结果正常对照组与模型组大鼠胰岛素敏感性指数(K_(ITT)值)分别为5.8±s 0.5和2.8±0.9,模型组明显低于正常对照组(P<0.01)。与模型组比较,孜亚比提片高、低剂量组均可降低T2DM大鼠的空腹血糖(FBG)和血清胆固醇(TC)水平,能提高高密度脂蛋白胆固醇(HDL-C)水平,差异有显著意义(P<0.05);孜亚比提片高剂量组可提高空腹血清胰岛素水平,差异具有显著意义(P<0.05);孜亚比提片高、低剂量组均可使胰岛素分泌指数增大(P<0.05)。结论孜亚比提片能降低T2DM大鼠的FBG和TC水平,其降血糖机制可能是通过促进胰岛素分泌、增加细胞对葡萄糖的利用而起作用的。     

运用PDCA管理方式对居家糖尿病患者胰岛素注射管理前、后血糖控制及生活质量的影响

目的 通过PDCA的管理方法,评估对糖尿病患者胰岛素注射管理前、后血糖控制及生活质量的影响.方法 选取该院2015年1-3月门诊注射胰岛素糖尿病患者100例,分成两组.治疗组患者使用PDCA管理方法加强进行教育,分析危险因素,制定个性化的治疗计划,并进行3个月的跟踪调研,对照组则按常规治疗并门诊随访.治疗组患者采用SF-36糖尿病简易生活质量量表评估.统计患者各个相关因素,并进行综合分析.结果 经过PDCA管理后的治疗组患者,在治疗前、后的胰岛素管理和知识方面、生活质量方面均有显著的提升.而在血糖控制方面,治疗组优于对照组(P＜0.001).结论 通过PD-CA的管理方法,居家糖尿病患者胰岛素注射管理前、后血糖控制及生活质量均有大幅优化与提升.     

硒对糖尿病小鼠血糖及糖代谢的影响

目的　研究硒对糖尿病小鼠血糖及糖代谢的影响 ,探讨硒降血糖的可能机制 ,为临床应用提供实验依据。方法　健康雄性昆明种小鼠 60只 ,随机分成 3组 ;正常对照组 (NC组 )、糖尿病组 (DM )组和糖尿病补硒组 (DM Se组 )。DM Se组每天给补硒液 3 0 0 μg kg ,持续 8周进行相关指标的生化检测。结果　实验结束时DM Se组小鼠血糖 ( 2 0 .4± 6.3 )mmol L较DM组 ( 4 5 .2± 3 .2 )mmol L明显降低( P <0 .0 5 )。DM Se组的全血谷胱甘肽过氧化物酶 (GSH Px)活性、肝硒含量和肝葡萄糖激酶 (GK)活性较DM组明显升高 (P <0 .0 5 ) ,而血浆丙二醛 (MDA)明显下降 (P <0 .0 5 )。结论　硒降血糖的可能机制是硒增加机体的抗氧化能力和硒的胰岛素样作用     

糖尿病患者泪糖浓度与血糖浓度的相关性

目的探讨正常人和糖尿病患者泪糖浓度和血糖浓度的相关性。方法 2型糖尿病(T2DM)患者75例85只眼(A组)和正常对照组28例28只眼(B组),以微量血糖仪测定两组空腹血糖,随即以微量采血管采集非刺激性泪液20μl并以高效液相色谱质谱联用法(HPLC-MS)测定泪糖。结果 A组泪糖明显高于B组[(0.460±0.204)mmol/L vs.(0.081±0.027)mmol/L](P<0.01)。A组泪糖与血糖呈直线正相关(r=0.870,P<0.01);B组泪糖与血糖无直线相关(r=0.229,P>0.05)。结论在糖尿病患者中,泪糖浓度可以作为一个反映血糖浓度的良好指标。     

Effect of isoproterenol on glucose turnover and insulin secretion in the normal dog

Infusion of epinephrine in the dog causes a sustained hyperglycemia without increasing plasma insulin, whereas infusion of isoproterenol causes a transient hyperglecemia and increased plasma insulin. To investigate the basis for these differences, rates of hepatic glucose production and overall glucose uptake were determined using a primer-constant infusion of [3-³H]glucose in normal dogs, and these were correlated with plasma insulin levels. Infusion of epinephrine (0.2 μg/kg/min) for 3 hr caused a prompt and persistent hyperglycemia. Concomitantly glucose production was increased but returned to normal by 90 min. Plasma insulin and glucose uptake did not increase. Isoproterenol infusion (0.2 μg/kg/min) for 3 hr caused a transient hyperglycemia. Glucose production and uptake were increased during the entire period. Plasma insulin was also elevated. The transient hyperglycemic response to isoproterenol, therefore, is not due to inadequate glucose production. Infusion of the beta-adrenergic blocker, propranolol, prevented the hyperglycemia and increased hepatic glucose production normally produced by isoproterenol.     

Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in non insulin dependent diabetes mellitus induced rats

Objective:

To study the effect of Trichosanthes cucumerina Linn. on non insulin dependent diabetes mellitus induced rats.

Materials and Methods:

Non Insulin Dependent Diabetes Mellitus (NIDDM) was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. NIDDM animals were treated with aqueous extract of Trichosanthes cucumerina (100 mg/kg/day) orally for six weeks. Parameters such as fasting blood glucose, Oral Glucose Tolerance Test (OGTT) and tissue glycogen content were evaluated.

Results:

Aqueous extract of Trichosanthes cucumerina significantly (P<0.01) decreased the elevated blood glucose of NIDDM induced rats. OGTT of NIDDM animals showed glucose intolerance. Blood glucose of diabetic animals reached peak at 45 min and remains high even after 2h. In case of Trichosanthes cucumerina treated group, the blood glucose reached peak level at 30 min, followed by decrease in glucose level up to 2h. The drug has significantly (P<0.01) reduced the postprandial blood glucose of diabetic animals. Glycogen content of insulin dependent tissues such as liver and skeletal muscle was found to be improved by 62% and 58.8% respectively with Trichosanthes cucumerina as compared to NIDDM control.

Conclusion:

Studies revealed that, Trichosanthes cucumerina possess antidiabetic activity. The drug improved the oral glucose tolerance of NIDDM subjects. Increase in tissue glycogen content indicates the effect of the drug on the uptake of glucose by the peripheral tissues to reduce insulin resistance of NIDDM.