Commentary: Inhibitors of mitochondrial respiratory chain in the treatment of type 2 diabetes

<正>Prevalence of type 2 diabetes has been increased worldwide following the high incidence of obesity and growing population of aging, which are two conditions for absolute energy excess with accumulation of TAG in the body and relative energy excess due to reduced energy expense, respectively. It appears that type 2 diabetes is a compensatory mechanism of body to energy excess through urine discharge of glucose.     

Metformin and oral contraceptive treatments reduced circulating asymmetric dimethylarginine (ADMA) levels in patients with polycystic ovary syndrome (PCOS)

There is a little information in literature about circulating asymmetric dimethylarginine (ADMA) concentrations in polycystic ovary syndrome (PCOS) and the results reported are discrepant. In this study, therefore, we aimed (1) to determine the circulating ADMA concentrations in 44 women with PCOS and 22 age- and BMI-matched healthy controls, (2) to evaluate its correlations with insulin resistance, gonadotrophins, and androgen secretion, and (3) to compare effects of metformin and ethinyl estradiol-cyproterone acetate (EE/CPA) treatments on circulating ADMA concentrations. In conclusion, our data indicate that circulating ADMA concentrations in non-obese, non-hypertensive and young women with PCOS are significantly higher than healthy controls and they improved by a 3-month course of metformin and oral contraceptive treatments.     

二甲双胍和罗格列酮对肥胖型PCOS治疗作用的对照性研究

目的观察罗格列酮和二甲双胍联合氯米芬治疗肥胖型多囊卵巢综合征患者的内分泌改善及生殖功能的临床疗效。方法50例肥胖型PCOS患者分别给予罗格列酮4mg/d和二甲双胍1500mg/d联合氯米芬100mg/d,治疗3个月,比较治疗前后体重指数、内分泌参数、腰臀比和Hom a IR的变化。结果用罗格列酮治疗后排卵率为88%,周期排卵率为64.29%,优势卵泡平均个数为1.8±0.8个,妊娠率为56%,而用二甲双胍治疗后分别为72%、54.84%、1.1±0.6个、48%。两者治疗后能使LH、LH/FSH、T的血清浓度明显下降,SHBG的浓度明显上升,Hom a IR明显改善。结论罗格列酮和二甲双胍联合氯米芬治疗肥胖型多囊卵巢综合征疗效可靠。二甲双胍有降低体重作用、价格便宜,适用于肥胖型P-COS伴胰岛素抵抗不严重者;罗格列酮在胰岛素增敏作用优于二甲双胍,适用于胰岛素抵抗较严重的PCOS患者。     

二甲双胍联合紫杉醇对人乳腺癌细胞凋亡及AMPK信号通路的影响

目的:探索二甲双胍联合紫杉醇对乳腺癌MCF-7细胞活力和凋亡的影响及其可能的机制。方法:采用不同浓度(2、5、10、20、40和80 mmol/L)二甲双胍作用于体外培养的MCF-7细胞,MTT法检测细胞的活力。采用2 mmol/L二甲双胍和2. 4 mg/L紫杉醇单独或联合处理细胞,并加入一磷酸腺苷活化的蛋白激酶(AMPK)信号转导通路抑制剂compound C。实验分为对照组、二甲双胍组、紫杉醇组、联合组和联合+compound C组;流式细胞术检测细胞的凋亡率,采用RT-qPCR和Western blot法检测Bax、Bcl-2和caspase-3的mRNA和蛋白表达量,Western blot检测AMPK和P21蛋白的表达量。结果:不同浓度二甲双胍(2、5、10、20、40和80 mmol/L)显著抑制乳腺癌细胞的活力(P 0. 05),且具有一定浓度依赖性。与对照组相比,2 mmol/L二甲双胍和2. 4 mg/L紫杉醇单独或联合均可显著抑制细胞活力并诱导其凋亡(P 0. 05),显著下调Bcl-2水平(P 0. 05),上调Bax和caspase-3水平(P 0. 05),促进AMPK和P21蛋白表达。联合使用的效果优于单独使用。加入AMPK抑制剂可削弱此作用。结论:二甲双胍联合紫杉醇可抑制乳腺癌MCF-7细胞活力,诱导其凋亡。此作用与激活AMPK信号转导通路并调节细胞凋亡信号通路有关。     

多囊卵巢综合征患者子宫内膜mPGES-1和COX-2表达的研究

目的:探讨多囊卵巢综合征(PCOS)患者膜结合型前列腺素合酶-1(mPGES-1)和环氧合酶-2(COX-2)在子宫内膜组织的表达及临床意义。方法:选择2005年6月至2007年6月华北煤炭医学院生殖内分泌门诊诊断为PCOS的患者21例为PCOS组,卵巢功能正常的不孕患者20例为对照组。PCOS组采用二甲双胍/达英-35联合治疗。病例均测体重、身高、性激素六项及75g葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)。并于月经干净3～5天(闭经患者确认为卵泡期)取子宫内膜组织,采用免疫组织化学技术检测PCOS组治疗前后及对照组中mPGES-1和COX-2的表达。结果:PCOS组患者BMI、HOMA-IR、空腹胰岛素(I0)、75g葡萄糖负荷后2h胰岛素(I120)及T均明显高于对照组患者(P均<0.05);治疗前PCOS组mPGES-1和COX-2在子宫内膜的表达显著高于对照组(P<0.01),治疗后两因子的表达与治疗前比较明显下降(P<0.01)。结论:PCOS患者子宫内膜可能处于一种慢性炎症状态,子宫内膜mPGES-1和COX-2过度表达可能是导致患者子宫内膜异常增生和不孕的原因之一,二甲双胍/达英-35联合应用可逆转该炎症状态,可能有利于孕卵着床和预防子宫内膜癌发生。     

二甲双胍在妊娠期应用的研究进展

近年研究不断证实二甲双胍治疗妊娠期糖尿病的有效性。在近期安全性上,研究发现二甲双胍不增加不良妊娠结局的发生率,且较胰岛素相比,可减少母体孕期增重和低血糖发生率;在远期安全性上,随访研究尚未发现二甲双胍相关的不良结局。本文主要介绍二甲双胍妊娠期使用的有效性和安全性证据,并对国内外指南的建议进行总结,以及对二甲双胍具体用药方案进行说明。     

Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes

AGE inhibitors may act by various mechanisms at different steps of advanced glycation endproduct (AGE) formation (depending on oxidative stress and/or carbonyl stress) and AGE-mediated damage: trapping of reactive dicarbonyl species; antioxidant activity by transition metal chelation; other antioxidant activity including free radical scavenging; AGE cross-link breaking; AGE receptor (RAGE) blocking; RAGE signaling blocking; glycemia reduction by anti-diabetic therapy; aldose reductase inhibition; shunting of trioses-P towards the pentose-P pathway by transketolase activation. Most of the inhibitors have several sites of action. Practically one can distinguish drugs specifically developed as AGE inhibitors or AGE breakers; RAGE and receptor signaling blockers; other therapeutic compounds which were found subsequently to possess also AGE inhibitor activity, including dietary antioxidants. Encouraging results obtained in studies of various AGE inhibitors, conducted in vitro and in diabetic animals, are summarized in this review. However most of the clinical trials have been more or less disappointing, in part because of side effects; the long-term therapeutic interest of the most recently developed AGE inhibitors or breakers remains to be demonstrated in diabetes.     

八味丸方药对代谢综合征患者治疗效应的临床观察

目的：考察八味丸方药（汤剂）对代谢综合征患者血糖、血压、血脂、血胰岛素及血浆过氧化脂质等的影响。方法：将60例代谢综合征患者随机分为实验组和对照组,对照组服卡托普利和二甲双胍,实验组在此基础上加服八味丸方汤剂,疗程印天,观察两组治疗前后血糖、血压、血脂、血胰岛素及血浆过氧化脂质等指标变化。结果：实验组有效率明显高于对照组（p〈0．01）。与对照组相比,实验组治疗后的血糖、血压、血脂、血胰岛索及血浆过氧化脂质等指标的改善更明显（p〈0．05or p〈O．01）。结论：本研究结果提示,八味丸方药对代谢综合征的降糖、降脂、降胰岛素和降压作用主要是通过改善IR而实现的;八味丸方药较好的改善IR及相关病理生理改变的作用,可能与其降低血浆过氧化脂质有关。     

二甲双胍联合炔雌醇环丙孕酮片对多囊卵巢综合征患者性激素和胰岛素水平的影响

目的:研究二甲双胍联合炔雌醇环丙孕酮片对多囊卵巢综合征(Polycystic ovarian syndrome,PCOS)患者性激素和胰岛素水平的影响。方法:选取2018年3月至2019年10月于我院就诊的PCOS患者135例,按照随机数字表法分为两组,对照组患者67例予以炔雌醇环丙孕酮片(每天1片)口服,研究组68例在对照组的基础上增加二甲双胍(每天0.85 g)口服。治疗3个疗程后,观察两组患者临床疗效、性激素水平、胰岛素水平、自然受孕率、不良反应。结果:研究组患者治疗后的临床有效率、受孕率明显高于对照组(P<0.05)。治疗后研究组黄体生成素(Luteinizing hrmone,LH)、睾酮(Testosterone,T)、卵泡刺激素(Follicle-stimulating Hormone,FSH)、胰岛素抵抗指数(Homeostasis model assessment insulin resistance,HOMA-IR)、空腹胰岛素(Fasting serum insulin,FINS)、空腹血清葡萄糖(Fasting plasma glucose,FPG)均显著低于对照组(P<0.05),雌二醇(Estradiol,E2)显著高于对照组(P<0.05)。两组患者不良反应发生率无显著差异(P>0.05)。结论:二甲双胍联合炔雌醇环丙孕酮片应用于PCOS患者可通过纠正性激素紊乱、改善胰岛素抵抗来提高临床疗效及自然受孕率,可临床推广。