The Effect of K-ATP Channel Blockage During Erythropoietin Treatment in Renal Ischemia-Reperfusion Injury

ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection but these channel activations have role in cytoprotective role of EPO in the renal ischemia reperfusion (IR) damage is still unknown. For this purpose rats were pretreated with EPO (500 IU/kg) and/or K-ATP channel blocker glibenclamide (40mM/kg) i.p. before bilateral renal IR damage. Renal tissues were used for histological examination and measurement of caspase-3 and TNF-α levels. Renal functions were evaluated by glomerular filtration rate (GFR) fractional excretion of sodium (FENa) and potassium (FEK). Renal TNF-α and caspase-3 levels were decreased in both glibenclamide and EPO-treated IR rats compared to untreated rats. The protection afforded by the pretreatment with EPO alone was greater than that of administering glibenclamide alone. Application of glibenclamide at the same time partly abolished the cytoprotective effect of EPO treatment. K-ATP mediated cytoprotection is not the main mechanism of protective effect of EPO.     

Extrapancreatic and pancreatic actions of glibenclamide in rats

Summary The aim of this study was to investigate the influence of glibenclamide on insulin release via insulinotropic gut factors and via a direct action on the pancreas. Maximum peripheral IRI levels appeared 1 minute after intragastric administration of the minimal effective dose of glibenclamide to rats. The corresponding drug levels were high (600 ng/g) in the duodenal mucosa, but low (2 ng/ml) in the peripheral serum. These concentrations were too low to cause insulin release by direct action on the pancreas. Intragastric glibenclamide increased the amount of duodenal insulin releasing activity (DIRA) in the mucosa immediately after drug administration. When glibenclamide was dissolved in plasma at a high concentration (1 g/ml) and then injected into the coeliac trunk of an in-situ rat pancreas preparation, no additional effect on portal IRI levels was measured as compared with injection of serum alone. In contrast significant IRI release was noticed when glibenclamide was dissolved in serum (1 g/ml) of rats pretreated with the drug intragastrically. The plasma of pretreated rats without addition of glibenclamide was ineffective. The results suggest that glibenclamide may have two effects, one releasing insulin at the pancreas directly, and the other inducing the release of a gastrointestinal factor which amplifies the first effect. Neither glibenclamide nor the factor alone can provoke an IRI release under physiological conditions. The possible importance of these findings for the regulation of insulin secretion is discussed.Presented at the 11th EASD Congress, Munich, September 1975     

二甲双胍对2型糖尿病模型大鼠尿nephrin排泄的影响

目的:观察二甲双胍对2型糖尿病模型大鼠尿nephrin(UNE)排泄的动态影响,探讨二甲双胍对糖尿病肾小球足细胞的保护作用?方法:将高脂膳食联合小剂量链脲佐菌素(streptozotocin,STZ)诱导的2型糖尿病大鼠随机分为3组:糖尿病模型组?二甲双胍干预组?优降糖干预组,并设正常对照组?干预前后监测血糖(BG)以及尿白蛋白(UALB)和尿nephrin排泄?8周末糖化血红蛋白(HbA1c)的变化?结果:①3组糖尿病大鼠BG及HbA1c均明显高于正常组(P < 0.05);经二甲双胍和优降糖干预后,4?8周末2组BG和HbA1c均明显低于2型糖尿病模型组(P < 0.05),但差异无统计学意义(P > 0.05);②4?8周末各糖尿病大鼠尿白蛋白/肌酐比(UACR)明显高于正常组(P < 0.05);与2型糖尿病模型组比较,二甲双胍和优降糖组UACR值明显降低(P < 0.05),4周末,两干预组间无显著性差异(P > 0.05),8周末,两组间差异有统计学意义(P < 0.05);③0?2周末,4组大鼠尿nephrin/肌酐比(UNER)差异无统计学意义,4?8周末,各糖尿病大鼠UNER均明显高于正常组(P < 0.05),二甲双胍和优降糖干预组UNER明显低于糖尿病模型组(P < 0.05),且二甲双胍组低于优降糖组(P < 0.05);④Pearson相关分析显示UNER与UACR存在正相关(r=0.846,P < 0.05)?结论:二甲双胍可以降低糖尿病肾病大鼠尿nephrin的排泄,提示对肾小球足细胞可能存在保护作用,该作用不完全依赖于血糖的降低?     

来得时联合拜唐平治疗初发Ⅱ型糖尿病疗效观察

目的观察来得时联合拜唐平治疗初发Ⅱ型糖尿病的临床疗效，并作安全性评价。方法将符合初发Ⅱ型糖尿病纳入标准病例90例，按入院顺序随机分为治疗组45例与对照组45例，对照组予以诺和灵30R治疗，治疗组给予来得时联合拜唐平治疗，比较两组的疗效，以及两组治疗前后各项实验室指标的变化情况。结果治疗组总有效率明显优于对照组（P〈O．05），且治疗组在降低空服血糖、餐后2小时血糖及糖化血红蛋白水平方面均明显优于对照组（P〈0．05或P〈0．01）。治疗组低血糖发生率明显低于对照组，差异有统计学意义（P〈0．05）。结论来得时联合拜唐平治疗初发Ⅱ型糖尿病疗效确切，安全有效，低血糖发生率低，值得临床推广应用。     

A systematic review of the safety of probiotics

Introduction: Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is associated with several adverse outcomes over the short- and long-term for both mother and offspring. Standard treatment for GDM consists of insulin injections. Oral hypoglycemic agents (OHAs), on the other hand, are still the subject of controversy. Although OHAs are seemingly as efficient as insulin and may provide better quality of life, congenital malformations and unknown long-term effects are still feared.

Areas covered: Recent data on the pharmacokinetics of two OHAs (glyburide and metformin) and their clinical use for GDM are reviewed, with a focus on clinical trials and observational studies comparing insulin with glyburide or metformin (1960 – 2010). The review will provide a comprehensive overview of the pros and cons of OHA usage, an appreciation of OHAs' efficiency for the purpose of controlling glycemia and embryogenetic basics relating to congenital malformations.

Expert opinion: While insulin treatment is an effective therapy for controlling maternal glycemia, it nevertheless requires sufficient education and skills on the part of the patient to manage properly and may cause hypoglycemia, fear and anxiety. Oral treatment as a more user-friendly alternative may thus facilitate the control of GDM in some patients.     

Mechanism of the vasodilatory action of nicorandil on coronary circulation in dogs

Summary Nicorandil possesses hybrid properties as a nitrate and a potassium (K) channel opener. We have previously reported that large coronary arteries responded to nicorandil at low plasma concentrations, while dilatation of small coronary arteries only occurred at higher plasma concentrations (above 200 ng/ml) in chronically instrumented dogs. In this study we examined the effects of intravenous nicroandil on epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) in the absence and presence of glibenclamide, a K⁺ channel blocker, as well as the effects of nitroglycerin and cromakalim as reference drugs. The increase in CBF induced by nicorandil and cromakalim was significantly suppressed by glibenclamide. However, the increase in CoD induced by nicorandil and nitroglycerin was not suppressed by glibenclamide. These findings suggest that nicorandil-induced dilatation of the large coronary arteries was related to its nitrate action, while nicorandil-induced dilatation of the small coronary arteries was closely related to its effect as a K⁺ channel opener. In addition, the former response to nicorandil occurred at low concentrations, while the latter occurred at higher concentrations.