2007—2011年我院降血糖药应用情况分析

目的了解我院降血糖药的使用情况。方法用DDD分析法和金额排序法对2007—2011年降血糖药使用情况进行分析。结果我院口服降血糖药使用金额增长迅速;瑞格列奈、吡格列酮及阿卡波糖位列使用金额前3位;按用药频度(DDDs)排序前3位是二甲双胍、吡格列酮和瑞格列奈;人胰岛素及胰岛素类似物的使用大幅上升。结论我院口服降血糖药品种稳定,应用基本合理;胰岛素及胰岛素类似物的使用符合临床胰岛素早期强化治疗的趋势。     

2011年我院门诊抗糖尿病药使用分析

目的了解医院门诊口服糖尿病用药情况,为临床合理用药提供参考。方法对2011年抗糖尿病药物的应用品种、销售金额、用药频度（DDDs）进行统计、分析。结果在5类抗糖尿病药物中,α-葡萄糖苷酶抑制剂和促进胰岛素分泌剂分别居于销售前2位;在调查的12种药物中,瑞格列奈（孚来迪）,二甲双胍（国产）,吡格列酮使用频率较高。结论门诊抗糖尿病药使用基本合理。     

我院2006～2008年抗糖尿病药利用分析

目的：分析2006～2008年我院抗糖尿病药的使用情况和变化趋势,以促进临床更合理使用药物。方法：运用药库计算机管理系统对我院2006～2008年抗糖尿病药的品种、消耗量、用药金额、用药频度（DDDs）、日均费用（DDDc）及排序进行统计分析。结果：我院抗糖尿病药主要为口服降糖药,DDDs占54．78％,抗糖尿病药消耗金额逐年上升,口服降糖药用药频率排在前3位的分别是二甲双胍、瑞格列奈、阿卡波糖,注射降糖药70-30混合人胰岛素其DDDs排序三年稳居首位,结论：我院抗糖尿病药品种齐全,各种生物合成人胰岛素和新型口服抗糖尿病药的用量将不断增加,用药基本合理。     

2010-2012年浙江省德清县第三人民医院抗高血压药、治疗糖尿病药和血脂调节药用药分析简

目的：分析浙江省德清县第三人民医院2010-2012年高血压、糖尿病和高脂血症（三类疾病）用药情况及用药趋势,为临床合理用药提供参考.方法：对本院2010-2012年抗高血压药、治疗糖尿病药和血脂调节药用药的品种、用药金额等进行回顾性分析.结果：2010-2012年本院抗高血压药、治疗糖尿病药和血脂调节药的用药金额逐年增加,其中用药金额第一、二位的抗高血压药是厄贝沙坦片和氨氯地平片;治疗糖尿病药是精蛋白生物合成人胰岛素注射液和瑞格列奈片;血脂调节药是阿托伐他汀钙片和辛伐他汀片.2010、2011和2012年3类药物用药金额共占该年全院用药金额的3.51％、4.36％和4.98％;其中隶属国家基本药物的用药金额分别占48.09％、40.92％和37.01％.结论：抗高血压药、治疗糖尿病药和血脂调节药用药量逐年增加,隶属国家基本药物的用药金额占比逐年降低,本院整体用药趋势与国家卫生部医院管理合作项目医院统计结果相近.     

新型降血糖药瑞格列奈

瑞格列奈是第一个用于治疗糖尿病的苯甲酸衍生物 ,能有效地刺激胰岛素的分泌 ,降低空腹和餐后血糖水平。起效迅速 ,T12 短 ,给药灵活 ,不良反应少。本文对其药理作用、药物动力学和临床应用等方面作一综述。     

瑞格列奈对吡格列酮及其主要活性代谢物在健康人体的药代动力学影响

目的 研究瑞格列奈(短效促胰岛素释放剂)对吡格列酮(胰岛素增敏剂)及其主要活性代谢物在健康人体中的药代动力学影响.方法 采用随机交叉试验设计,将12名男性健康受试者随机分为吡格列酮单药给药组和吡格列酮与瑞格列奈片合并给药组,清洗期为2周.采用HPLC-MS法测定吡格列酮及其代谢产物M-Ⅳ、M-Ⅲ的血药浓度.结果 合并瑞格列奈给药后,PIO、M-Ⅳ、M-Ⅲ的AUC0-τ分别为(6.15±2.71),(12.88±5.16),(5.72±3.06)μg·h·mL-1;Cmax分别为(626.77±208.21),(272.24±153.76),(132.04±78.42)ng·mL-1;tmax分别为1.0(0.5～3.0),12.0(12.0～ 72.0),12.0(12.0～ 15.0)h,与吡格列酮单药给药组相比,均无显著性改变(P>0.05).吡格列酮单药和吡格列酮与瑞格列奈片合用在健康人体的药代动力学行为相近.结论 瑞格列奈对吡格列酮及其主要活性代谢物在健康人体的药代动力学无显著影响.     

抗糖尿病药应用分析

目的：评价南京市第三医院抗糖尿病药的应用现状及变化趋势,为临床用药提供参考。方法：对我院2007--2009年抗糖尿病药的销售金额、各生产厂家药品所占份额等进行统计分析。结果：我院抗糖尿病药销售金额逐年上升,2008年、2009年分别比上一年增长20．56％、32．83％,其中磺酰脲类、格列奈类胰岛素分泌促进剂、胰岛素及其类似物2009年增幅分别达到41．20％、37．61、34．29％。结论：抗糖尿病药市场需求潜力大,其在我院的销售呈快速增长趋势,高效、安全、依从性好的药物受到临床青睐。     

2005-2009年东莞市东华医院抗糖尿病药使用情况分析

目的：分析东莞市东华医院2005—2009年抗糖尿病药的使用情况及用药趋势。方法：用金额排序法及DDD分析法统计5年来抗糖尿病药在我院的消耗情况、品种分布及用药费用,作为分析判断药物使用情况指标,分析临床糖尿病患者的用药状况。结果：近5年来,我院抗糖尿病药用药金额和用药频率（用药/人次）均有大幅度的增长（口服及注射剂用药金额增幅分别为132.04%和144.46%,且用药频率增幅分别为126.40%和144.46%）。用药金额排序前3位为α-糖苷酶抑制剂、磺酰脲类和双胍类;用药频率（用药/人次）排序前3位为α-糖苷酶抑制剂、磺酰脲类和促进胰岛素分泌剂,阿卡波糖使用最多且同步性好。胰岛素使用均在20%以下,以短效胰岛素使用为主。结论：5年间糖尿病患者口服抗糖尿病药使用较多,其中α-糖苷酶抑制剂的使用占主导地位,胰岛素使用有待提高     

瑞格列奈在2型糖尿病治疗中的应用

瑞格列奈为一种氨甲酰基苯甲酸类衍生物．其作用机制与磺酰脲类药物相似,均作用于B细胞上磺酰脲类药物受体,引起K-（KAT1）通道关闭和Ca^2＋通道开放．最终促进胰岛素的分泌,所不同的是与suR的结合位点不同,能改善胰岛素第1相分泌,在模拟餐时正常胰岛素分泌模式、降低餐后血糖水平方面有着杰出的表现。本文对瑞格列奈从药理学作用机制、药代动力学特点、在2型糖尿病中的应用．安全性与耐受性、适应证和禁忌证等方面进行综述。     

瑞格列奈在健康人体的药代动力学和药效动力学研究

目的：研究瑞格列奈的药代动力学和药效动力学。方法：19名健康男性受试者单剂量口服4 mg瑞格列奈片,采用HPLC-MS-MS法测定给药后不同时间瑞格列奈的血药浓度,用快速血糖仪测定不同时间指尖血的血糖。利用DAS 2.0计算药动学参数和进行统计分析。结果：瑞格列奈体内过程符合一室开放模型,达峰浓度Cmax为（83.1±23.6）μg/L;达峰时间tmax为（0.71±0.21）h;AUC0-8为（97.1±37.8）μg·L^-1.h;t1/2为（1.6±0.7）h。给药后血药浓度水平升高,血糖随之下降,于给药后1 h最低,达（3.0±0.65）mmol/L。结论：瑞格列奈起效迅速、作用持续时间短,适合餐后血糖调节,用于通过运动和控制饮食治疗无效的2型糖尿病患者。     

Effect of diltiazem on insulin secretion. II. Experiments on perfused rat pancreas, anesthetized dogs and conscious rats.

Effect of diltiazem on insulin secretion was investigated in the perfused rat pancreas. Experiments were also carried out in anesthetized dogs and conscious rats with and without glucose loading. In the perfused rat pancreas, diltiazem reduced both glucose- and tolbutamide-induced insulin secretion and these effects of diltiazem were reversed with removal of the compound. Inhibition of the glucose-induced insulin secretion caused by diltiazem was counteracted by increasing the concentration of calcium ion. In experiments on intact animals, diltiazem at vasoactive doses produced no significant influence on the basal level of plasma insulin or glucose-induced insulin secretion. These data taken together with findings in previously reported work suggest that diltiazem reduces insulin secretion from pancreatic B-cells in vitro possibly by the calcium-antagonistic property, while the compound exhibits practically no inhibitory action on the insulin secretion in vivo.     

灵菊七水提物的降糖作用及促胰岛素分泌作用研究

目的观察灵菊七水提物的降糖作用及对胰岛细胞分泌胰岛素的影响。方法采用四氧嘧啶（70mg·kg^-1）诱导的糖尿病模型小鼠和正常小鼠,连续给药7d后,观察灵菊七水提物（2．5mg·kg^-1、5mg·kg^-1和10mg·kg^-1）对血糖、血清胰岛素水平和糖耐量的影响;采用MIN6胰岛细胞株,观察灵菊七水提物对胰岛素分泌的影响。结果在给药7d后,灵菊七水提物可明显降低糖尿病小鼠的血糖水平,并可明显降低正常小鼠和糖尿病小鼠的糖耐量,促进胰岛素的分泌;灵菊七水提物对葡萄糖（16．7mmol·^-1）刺激下胰岛素的分泌明显具有促进作用。结论灵菊七水提物可通过促进胰岛素分泌来降低血糖。     

胰岛素、地塞米松和米非司酮对PC12细胞合成和分泌儿茶酚胺的影响及机制探究

目的：考察胰岛素、地塞米松及米非司酮对PC12细胞合成和分泌儿茶酚胺的影响。方法：常规培养及用100 nmol/L的胰岛素（造成胰岛素抵抗模型）培养PC12细胞24小时,单用及合用胰岛素、地塞米松和米非司酮作用于PC12细胞24小时,用荧光检测法检测缓冲液及裂解液中儿茶酚胺的含量。结果：在正常组和模型组中,高浓度的胰岛素（≥100 nmol/L）和地塞米松（≥3μmol/L）单用时,PC12细胞的儿茶酚胺合成和分泌均显著增加（P〈0.01）,而米非司酮单用对PC12细胞的儿茶酚胺合成和分泌无显著影响;胰岛素与地塞米松合用时,随地塞米松浓度的增加,PC12细胞的儿茶酚胺的分泌增加,且当地塞米松浓度高于3μmol/L时,PC12细胞的儿茶酚胺分泌量与不加用地塞米松相比有显著性差异（P〈0.01）;胰岛素、地塞米松和米非司酮合用时,随米非司酮浓度的增加,PC12细胞的儿茶酚胺分泌逐渐减少。在模型组中,胰岛素、地塞米松和米非司酮单用及合用对胞内儿茶酚胺含量均无明显影响。结论：胰岛素和糖皮质激素可显著增加儿茶酚胺的合成和分泌,米非司酮则能抑制这种增强效应。     

去乙酰化酶SIRT1对胰岛B细胞株MIN6分泌功能的影响及其机制研究

目的观察沉默信息调节因子1（SIRT1）对小鼠胰岛B细胞株MIN6胰岛素分泌功能的影响,并初步探讨其机制。方法应用逆转录聚合酶链反应（RT-PCR）法检测SIRT1及其下游肝脏X受体（LXRs）的mRNA在MIN6细胞中的表达,应用酶链免疫吸附测定法（ELISA）分别检测SIRT1激动剂白藜芦醇（resveratrol）和SIRT1抑制剂sirtinol对MIN6细胞胰岛素分泌影响的量效与时效关系及SIRT1下游调控基因LXRs抑制剂22（S）-羟化胆固醇（22-S-HC）对MIN6细胞胰岛素分泌功能的影响。结果 SIRT1激动剂resveratrol能够明显的促进MIN6细胞的胰岛素分泌,SIRT1抑制剂sirtinol则对MIN6细胞的胰岛素分泌具有一定的抑制作用,且均呈一定程度的时间-剂量依赖关系。SIRT1的活性变化不会引起LXRs的mRNA表达变化。SIRT1下游调控因子LXRs的抑制剂22-S-HC能够部分拮抗白藜芦醇对MIN6细胞的胰岛素分泌的促进作用。结论 SIRT1的活性对于MIN6细胞的胰岛素分泌具有明显的正相关调节作用,其机制可能与SIRT1下游的核转录因子LXRs的活性有关。     

Effects of amidated rat islet amyloid polypeptide on glucose-stimulated insulin secretion in vivo and in vitro in rats

Amidated rat islet amyloid polypeptide (IAPP) is a constituent of secretory granules in islet B-cells. We examined its influence on glucose-stimulated insulin secretion in rats. In vivo, intravenous infusion of IAPP (68 pmol/min) did not affect glucose-stimulated insulin secretion. In vitro, IAPP slightly inhibited glucose (8.3 mM)-stimulated insulin secretion from isolated rat islets at the high dose level of 10(-5) M but not at the lower dose levels. We conclude that the IAPP is not involved in the normal regulation of insulin secretion.     

Effect of reserpinization on insulin secretion in the rat

Reserpine-induced supersensitivity to the insulin-releasing action of a beta-adrenergic agonist, isoprenaline, and of glucose was studied in vivo and in vitro. The subcutaneous injection of rats with reserpine (0.05 to 10 mg kg-1) enhanced the action of isoprenaline on insulin secretion. ED50 of isoprenaline for insulin secretion was changed little after reserpinization, whereas maximum effect of the beta-agonist was enhanced by pretreating rats with reserpine. Glucose-stimulated insulin secretion was also enhanced in the reserpinized rats. Pancreases isolated from the reserpinized rats secreted more insulin in response to phentolamine in the presence of glucose and isoprenaline. These results suggest that the supersensitivity in insulin secretion induced by reserpine may be non-specific.     

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.     

不同浓度的葡萄糖对INS-1细胞cAMP生成与胰岛素分泌的影响

目的了解葡萄糖对INS-1细胞cAMP生成与胰岛素分泌的影响。方法用不同浓度的葡萄糖（2．8、7．5、15mmol／L）刺激INS-1细胞,作用30min后用ELISA方法检测cAMP与胰岛素的变化情况。结果葡萄糖浓度的提高对INS-1细胞cAMP生成与胰岛素分泌有明显的刺激作用（P〈0．05）,且表现出一定的浓度相关性。结论葡萄糖浓度提高能诱导INS-1细胞cAMP生成及促进其胰岛素分泌功能。     

Effect of pertussis pretreatment on plasma glucose and insulin responses to lithium in rats.

1. Administration of lithium to rats causes a rise in plasma glucose and suppresses glucose-stimulated insulin secretion. These effects are blocked by the alpha 2-adrenoceptor antagonist, yohimbine. 2. Pretreatment of rats with Bordetella pertussis toxin resulted in a reversal of the usual plasma glucose and insulin responses to intravenously administered lithium (4 mEq kg-1). There was a slow fall in plasma glucose, while plasma insulin rose to 267 +/- 42% (+/- s.e.mean) of control values at 30 min. The effect of lithium on glucose-stimulated insulin secretion was also reversed; there was a marked increase in the insulin response which contrasted with the suppression seen in normal controls. 3. In perifused islets of Langerhans isolated from pertussis pretreated rats, the previously described inhibition by lithium of the second phase of glucose-stimulated insulin secretion from normal islets was almost completely abolished. 4. The results are consistent with the hypothesis that these effects of lithium are mediated by the influence of catecholamines on the islets. When the inhibitory effect of alpha 2-adrenoceptors is abolished by pertussis treatment, which blocks the action of the inhibitory guanine nucleotide-binding protein Gi, effects of beta-adrenoceptor stimulation predominate, leading to an increased secretion of insulin.     

Effects of alpha-adrenoceptor agonists and antagonists on insulin secreting cells and pancreatic blood vessels: comparative study

The effects of alpha-adrenergic drugs were studied on glucose-induced insulin secretion and effluent flow rate on the same preparation: the isolated perfused rat pancreas. An alpha 1-adrenoceptor agonist, phenylephrine 0.05 microM slightly decreased insulin secretion (-25%); this inhibition was counteracted by an alpha 2-adrenoceptor antagonist, yohimbine 0.6 microM. Phenylephrine evoked a fall in liquid flow rate (-13%) which was reversed by an alpha 1-adrenoceptor antagonist, prazosin 6 microM, but not by yohimbine. An alpha 2-adrenoceptor agonist, clonidine 0.01 and 0.05 microM decreased insulin secretion (-80%). This inhibition was reversed by yohimbine 0.6 and 6 microM respectively. Only the concentration of 0.05 microM clonidine evoked a fall (-25%) in liquid flow rate; this fall was counteracted by yohimbine 0.6 microM. In conclusion our results show that adrenergic inhibition of insulin secretion is mediated only by alpha 2-receptors whereas both types of adrenoceptors are implicated in the vasoconstrictor effect. The insulin inhibitory effect of adrenoceptor agonists is not related to vasoconstriction.