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Metformin: Pros and Cons 二甲双胍:利弊
Pub Date : 2021-08-30 DOI: 10.5772/intechopen.99815
Shalini Sivadasan, Muthukumaravel Subramanian, R. Aiyalu
Metformin was approved for the treatment of Type 2 Diabetes Mellitus in 1958 for UK, in 1972 for Canada and in 1995 by FDA in USA. Metformin is the drug of choice for patients who are obese and have type 2 diabetes mellitus. Though metformin was at first proven to treat hyperglycemia, many other uses of metformin are proven to be effective. It is also used for gestational diabetes mellitus, obesity, hyper secretion of ovarian androgen, poly-cystic ovary syndrome (PCOS), anti-psychotic therapy induced weight gain, cancer treatment and anti-aging. Metformin causes a decrease in appetite thus known to act on obesity. The other action of metformin is reduction of circulating levels of insulin and insulin like growth factor 1 (IGF-1) which is associated with anticancer action. There are ongoing researches about the effect of metformin on anti-aging properties and proved that metformin is linked with anti-aging factors. Three main factors that are related with aging are oxidation, glaciation and methylation. Metformin as all drugs, have unwanted effects as well. Many side effects of metformin are considered mild where lactic acidosis and vitamin B12 deficiency happens to be the major.
二甲双胍于1958年在英国被批准用于治疗2型糖尿病,1972年在加拿大被批准,1995年在美国被FDA批准。二甲双胍是肥胖和2型糖尿病患者的首选药物。虽然二甲双胍最初被证明可以治疗高血糖,但二甲双胍的许多其他用途也被证明是有效的。还用于妊娠期糖尿病、肥胖症、卵巢雄激素分泌过多、多囊卵巢综合征、抗精神病治疗引起的体重增加、癌症治疗和抗衰老。二甲双胍导致食欲下降,因此已知对肥胖起作用。二甲双胍的另一个作用是降低胰岛素和胰岛素样生长因子1 (IGF-1)的循环水平,这与抗癌作用有关。关于二甲双胍抗衰老作用的研究正在进行中,并证明二甲双胍与抗衰老因子有关。与老化有关的三个主要因素是氧化、冰川作用和甲基化。二甲双胍和所有药物一样,也有副作用。二甲双胍的许多副作用被认为是轻微的,乳酸酸中毒和维生素B12缺乏症恰好是主要的。
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引用次数: 0
Mechanisms of Action of Metformin 二甲双胍的作用机制
Pub Date : 2021-08-02 DOI: 10.5772/intechopen.99189
S. Mahmood
Metformin is the first-choice drug for treatment of type 2 diabetes notably those associated with obesity. It does not only reduce hyperglycemia, but also possesses pleiotropic effects opening the pave for numerous potential clinical applications. In this chapter we illustrate the various mechanisms of metformin action in reduction of hepatic glucose output, improvement of insulin action, restoration of fat metabolism and gut microbiome, reduction of inflammation, upregulation of antioxidant enzymes, and attenuation of tumor growth. Understanding of such mechanisms might propose further clinical applications for metformin.
二甲双胍是治疗2型糖尿病的首选药物,尤其是与肥胖相关的2型糖尿病。它不仅可以降低高血糖,而且具有多效性,为许多潜在的临床应用铺平了道路。在本章中,我们阐述了二甲双胍在降低肝脏葡萄糖输出、改善胰岛素作用、恢复脂肪代谢和肠道微生物群、减少炎症、上调抗氧化酶和抑制肿瘤生长方面的各种作用机制。对这种机制的理解可能会为二甲双胍的进一步临床应用提供建议。
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引用次数: 0
New Insight into Metformin Mechanism of Action and Clinical Application 二甲双胍作用机制及临床应用新认识
Pub Date : 2020-03-20 DOI: 10.5772/intechopen.91148
Yun Yan, K. Kover, W. Moore
Metformin is the first-line medication for Type 2 diabetes (T2D) treatment, and it is the only US FDA approved oral antidiabetic medication for pediatric patients with T2D 10 years and older. Metformin is also used to treat polycystic ovary syndrome (PCOS), another condition with underlying insulin resistance. The clinical applications of metformin are continuing to expand into other fields including cancer, aging, cardiovascular diseases, and neurodegenerative diseases. Metformin modulates multiple biological pathways. Its novel properties and effects continue to evolve; however, its molecular mechanism of action remains incompletely understood. In this chapter, we focus on the recent translational research and clinical data on the molecular action of metformin and the evidence linking the effects of metformin on insulin resistance, prediabetes, diabetes, aging, cancer, PCOS, cardiovascular diseases, and neurodegenerative diseases.
二甲双胍是治疗2型糖尿病(T2D)的一线药物,也是美国FDA唯一批准用于10岁及以上儿科T2D患者的口服降糖药物。二甲双胍也用于治疗多囊卵巢综合征(PCOS),这是另一种潜在胰岛素抵抗的疾病。二甲双胍的临床应用正在不断扩展到癌症、衰老、心血管疾病、神经退行性疾病等其他领域。二甲双胍调节多种生物途径。它的新特性和效果继续发展;然而,其分子作用机制尚不完全清楚。在本章中,我们将重点介绍二甲双胍分子作用的最新转化研究和临床数据,以及二甲双胍对胰岛素抵抗、前驱糖尿病、糖尿病、衰老、癌症、多囊卵巢综合征、心血管疾病和神经退行性疾病的影响。
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引用次数: 5
Potential Protective Effects of Metformin on Ocular Complications in Patients with Type 2 Diabetes 二甲双胍对2型糖尿病患者眼部并发症的潜在保护作用
Pub Date : 2020-02-25 DOI: 10.5772/intechopen.91263
J. Kusturica, A. Kulo, M. Rakanovic-Todic, L. Burnazović-Ristić, Sanita Maleškić
Diabetes mellitus (DM) as a chronic condition is a growing global problem. Its numerous complications, including ocular diseases, affect patients’ quality and length of life. Metformin is an effective, safe, and inexpensive first-line pharma-cotherapy for type 2 diabetes (T2D). The current evidence indicates metformin’s multiple sites of action and multiple molecular mechanisms leading to its beneficial impact on metabolism, inflammation, oxidative stress, aging, as well as to its cardiovascular, neurological, bone, and antiproliferative properties. These impacts are the result of its acting on adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Limited data suggest the protective role of metformin on microvascular ocular complications, including retinopathy, glaucoma, and age-related macular degeneration in patients with T2D. However, to confirm its mentioned protective and therapeutic effects, more large, randomized, double-blind, and placebo-controlled clinical studies are needed.
糖尿病(DM)作为一种慢性疾病是一个日益严重的全球性问题。它的许多并发症,包括眼部疾病,影响患者的生活质量和寿命。二甲双胍是治疗2型糖尿病(T2D)的有效、安全、廉价的一线药物辅助疗法。目前的证据表明,二甲双胍的多个作用位点和多个分子机制导致其对代谢、炎症、氧化应激、衰老以及心血管、神经、骨骼和抗增殖特性的有益影响。这些影响是其作用于腺苷单磷酸活化蛋白激酶(AMPK)依赖和AMPK独立途径的结果。有限的数据表明,二甲双胍对T2D患者的微血管眼部并发症(包括视网膜病变、青光眼和年龄相关性黄斑变性)具有保护作用。然而,为了证实其所提到的保护和治疗作用,还需要更多的大规模、随机、双盲和安慰剂对照的临床研究。
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引用次数: 5
Preventive and (Neo)Adjuvant Therapeutic Effects of Metformin on Cancer 二甲双胍对肿瘤的预防和(新)辅助治疗作用
Pub Date : 2020-02-18 DOI: 10.5772/intechopen.91291
Y. Jiao, Xiaochen Wang, Zhijun Luo
Metformin, the first-line antidiabetic drug, has become an attractive candidate in cancer therapy since retrospective clinical investigations reported that patients with type 2 diabetes receiving metformin had lower incidence of cancer than those with other glucose lowering drugs. In line with this, preclinical studies have demonstrated that the antitumor activity of metformin could proceed through several mechanisms. Thus far, metformin has been used in cancer prevention with reduced risk as consequence and treatment of various cancers as an adjuvant or neoadjuvant drug. Thus, existing data support the beneficial effects of metformin on many types of cancers such as reducing metastasis and mortality and improving pathological responses and survival rates. However, some reports do not support this and even show adverse effects. The discrepancy may be attributed to expression levels of its transporters or genetic background. Hence, this chapter briefly reviews information on the mechanism of metformin action and summarizes both completed and ongoing clinical trials in an attempt to evaluate the value of metformin in prevention and treatment of various cancer types.
二甲双胍作为一线降糖药物,已成为一个有吸引力的癌症治疗候选者,因为回顾性临床研究报道,2型糖尿病患者接受二甲双胍的癌症发病率低于其他降糖药物。与此相一致,临床前研究表明,二甲双胍的抗肿瘤活性可能通过几种机制进行。到目前为止,二甲双胍已被用于癌症预防,其结果是降低了风险,并作为辅助或新辅助药物治疗各种癌症。因此,现有数据支持二甲双胍对许多类型癌症的有益作用,如减少转移和死亡率,改善病理反应和生存率。然而,一些报告不支持这一点,甚至显示出不利影响。这种差异可能归因于其转运蛋白的表达水平或遗传背景。因此,本章简要回顾二甲双胍的作用机制,并总结已完成和正在进行的临床试验,试图评价二甲双胍在预防和治疗各种类型癌症中的价值。
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引用次数: 4
Metformin in Health Issues and Reproductive System 二甲双胍在健康问题和生殖系统中的应用
Pub Date : 2019-12-23 DOI: 10.5772/intechopen.90465
E. Pourmatroud
Metformin is one of oldest drug in reproductive medicine era; but most of times it is equal to polycystic ovary (PCO) syndrome especially obese patients. If it is still valuable or not, could have another health benefit or new fertility roles, and could be effective as well in male reproductive system will be discussed. According to increased rate of metabolic disorders and cardiovascular problems and cancers, there are several investigations on this old used drug. Those studies had been magnified its role as “the aspirin of current century,” which might have a promising role in longevity of the life. So, the chapter will be interesting.
二甲双胍是生殖医学时代最古老的药物之一;但大多数情况下与多囊卵巢综合征(PCO)相当,尤其是肥胖患者。它是否仍然有价值,是否有其他的健康益处或新的生育作用,以及是否在男性生殖系统中也有效,我们将讨论。根据代谢紊乱、心血管疾病和癌症发病率的增加,人们对这种老药进行了一些研究。这些研究夸大了它作为“本世纪的阿司匹林”的作用,它可能在长寿方面发挥着有希望的作用。所以,这一章会很有趣。
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引用次数: 1
Metformin Modulates the Mechanisms of Ageing 二甲双胍调节衰老机制
Pub Date : 2019-12-13 DOI: 10.5772/intechopen.89431
A. F. Cӑtoi, A. Andreicuț, D. Vodnar, K. Szabo, A. Corina, A. Arsene, S. Ștefan, R. Stoica, M. Rizzo
Living in a time when population is continuously ageing, the challenge and demand for assessing the age-related pathways, potential diseases and longevity have become of major interest. The pharmaceutical industry possesses huge resources in this field, mainly due to the recent discoveries of novel mechanisms of action of oldestablished, classical drugs. Here we find metformin, a well-established antidiabetic medicine but with new potential benefits, as the most recent reports quote. We present the main pathways of the possible implications of metformin in the modulation of ageing processes, evolution and diseases, focussing on its ageing counteraction, based on the latest scientifically based biochemical reports.
生活在人口不断老龄化的时代,评估与年龄有关的途径、潜在疾病和寿命的挑战和需求已成为人们的主要兴趣。制药工业在这一领域拥有巨大的资源,主要是由于最近发现了古老的经典药物的新的作用机制。在这里,我们发现二甲双胍,一种公认的抗糖尿病药物,但具有新的潜在益处,正如最近的报道所引用的那样。我们提出了二甲双胍在衰老过程、进化和疾病调节中的可能影响的主要途径,重点关注其衰老对抗,基于最新的科学生化报告。
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引用次数: 3
Metformin and Its Benefits in Improving Gut Microbiota Disturbances in Diabetes Patients 二甲双胍及其改善糖尿病患者肠道菌群紊乱的益处
Pub Date : 2019-10-23 DOI: 10.5772/intechopen.88749
Andra Iulia-Suceveanu, S. Micu, C. Voinea, Madalina Manea, D. Catrinoiu, L. Mazilu, A. Stoian, I. Parepa, R. Stoica, A. Suceveanu
The human gastrointestinal tract presents a vastly population of microorganisms, called the microbiota. The presence of these microorganisms offers many benefits to the host, through a range of physiological functions. However, there is a potential for these mechanisms to be disrupted condition, known as dysbiosis. Recent results are showing important associations between diabetes and the gut microbiota and how the intestinal flora can influence the prognosis of this illness. Microbial intestinal imbalance has been linked to alterations in insulin sensitivity and in glucose metabolism and may play an important role in the development of diabetes. Metformin is one of the most important and widely used first-line medications for the management of type 2 diabetes (T2D). It is a complex drug with multiple sites of action and multiple molecular mechanisms. In recent years, attention has been directed to other modes of action, other than the classic ones, with increasing evidence of a major key role of the intestine. By analysing the effects of metformin on the homeostasis of the microbiota of diabetes patients, our present topic becomes one of the major importance in understanding how metformin therapy can improve gut microbiota dysbiosis and thus provide a better outcome for this illness.
人类胃肠道中存在着大量的微生物,称为微生物群。这些微生物的存在通过一系列的生理功能为宿主提供了许多好处。然而,这些机制有可能被破坏,称为生态失调。最近的研究结果显示了糖尿病和肠道菌群之间的重要联系,以及肠道菌群如何影响这种疾病的预后。肠道微生物失衡与胰岛素敏感性和葡萄糖代谢的改变有关,并可能在糖尿病的发展中发挥重要作用。二甲双胍是治疗2型糖尿病(T2D)最重要和广泛使用的一线药物之一。它是一种具有多个作用位点和多种分子机制的复杂药物。近年来,随着越来越多的证据表明肠道起着重要的关键作用,人们的注意力已经转向了其他的作用方式,而不是传统的作用方式。通过分析二甲双胍对糖尿病患者微生物群稳态的影响,我们当前的主题成为理解二甲双胍治疗如何改善肠道微生物群失调从而为这种疾病提供更好结果的主要重要性之一。
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引用次数: 3
Metformin in Cervical Cancer: Metabolic Reprogramming 二甲双胍在宫颈癌中的作用:代谢重编程
Pub Date : 2019-09-11 DOI: 10.5772/intechopen.88930
M. Tyszka-Czochara, M. Majka
The reprogrammed metabolism plays a crucial role in intensively proliferating tumor cells to meet high energetic demands and adapt to metastasis and invasion. Metformin may counteract flexible metabolic phenotype of cervical cancer cells by restraining aerobic glycolysis ( Warburg effect ) and promoting mitochondrial-based metabolism. Metformin inhibits master oncogene c-Myc as well as hypoxia-induc-ible factor 1 (HIF-1 α ) and suppresses its downstream glycolytic regulatory enzymes and glucose transporters. Metformin targets bioenergetics of cervical cancer cells with aggressive phenotype and regulates the expression of enzymes controlling tricarboxylic acid cycle (TCA cycle) supplementation with substrates, glucose, and glutamine. The exposition of cervical tumor cells to Metformin alleviates their migratory capacity, restrains epithelial-to-mesenchymal transition (EMT) program implementation, and elucidates oxidative stress, which results in massive cell death due to apoptosis. The metabolic alterations caused by Metformin are specific to cancer cells. In summary, Metformin exerts antitumor effect in cervical cancer cells by regulating specific molecular targets in reprogrammed metabolism. Metformin selectively modulates metabolic pathways and thus may be potentially used in new precisely targeted therapeutic strategies for cervical cancer.
重编程代谢在肿瘤细胞密集增殖以满足高能量需求和适应转移和侵袭中起着至关重要的作用。二甲双胍可能通过抑制有氧糖酵解(Warburg效应)和促进线粒体代谢来抵消宫颈癌细胞的灵活代谢表型。二甲双胍抑制主癌基因c-Myc和缺氧诱导因子1 (HIF-1 α),并抑制其下游糖酵解调节酶和葡萄糖转运蛋白。二甲双胍靶向具有侵袭性表型的宫颈癌细胞的生物能量学,并调节控制三羧酸循环(TCA循环)与底物、葡萄糖和谷氨酰胺补充的酶的表达。子宫颈肿瘤细胞暴露于二甲双胍会降低其迁移能力,抑制上皮-间质转化(EMT)程序的实施,并阐明氧化应激,导致细胞凋亡导致大量细胞死亡。二甲双胍引起的代谢改变是癌细胞特有的。综上所述,二甲双胍通过调节重编程代谢中的特定分子靶点,在宫颈癌细胞中发挥抗肿瘤作用。二甲双胍选择性地调节代谢途径,因此可能潜在地用于新的精确靶向治疗宫颈癌的策略。
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引用次数: 1
Antitumoral Effects of Metformin in Ovarian Cancer 二甲双胍对卵巢癌的抗肿瘤作用
Pub Date : 2019-09-05 DOI: 10.5772/intechopen.88911
Maritza P. Garrido, M. Vega, C. Romero
In the last years, the antidiabetic drug metformin has received considerable attention in pursuing new drugs for anticancer treatments. Several reports have shown that metformin would have antitumor effects, not only attributable to its systemic effects but also due to direct effects on tumor cells. It has been proposed that metformin could be a suitable alternative for the treatment of gynecological cancers, such as ovarian cancer. This disease is characterized by high cell proliferation and angiogenesis potential, because ovarian cancer cells overexpress most oncogenic molecules including growth factors. The aim of the present chapter is to discuss the molecular mechanism by which metformin would affect tumor cells, with focus on epithelial ovarian cancer.
在过去的几年里,抗糖尿病药物二甲双胍在寻求抗癌新药方面受到了相当大的关注。一些报道表明,二甲双胍具有抗肿瘤作用,不仅由于其全身作用,而且由于对肿瘤细胞的直接作用。有人提出,二甲双胍可能是治疗妇科癌症(如卵巢癌)的合适选择。这种疾病的特点是高细胞增殖和血管生成潜力,因为卵巢癌细胞过度表达大多数致癌分子,包括生长因子。本章的目的是讨论二甲双胍影响肿瘤细胞的分子机制,重点是上皮性卵巢癌。
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引用次数: 3
期刊
Metformin [Working Title]
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