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Metformin HCl

现货
Catalog No.
B1970
抗糖尿病药物
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
10g
¥ 500.00
现货
50g
¥ 1,200.00
现货

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Background

Metformin HCl is one of the most effective and widely used therapeutics for treatment of type 2 diabetes. It selectively lowers the hepatic gluconeogenesis without rising insulin production, causing weight gain or hypoglycemia. [1]

AMPK (5'AMP-activated protein kinase) acts as a metabolic master switch regulating several intracellular systems including the cellular uptake of glucose, the β-oxidation of fatty acids and the biogenesis of GLUT4 (glucose transporter 4) and mitochondria.

In hepatocytes, AMPK was activated by metformin, followed by decreased ACC (acetyl-CoA carboxylase) activity, induction of fatty acid oxidization and suppression of lipogenic enzyme expression.[2] Metformin also inhibited mGPD (mitochondrial lycerophosphate dehydrogenase),a redox shuttle enzyme, leading to an altered hepatocellular redox state, decreased conversion of lactate and reduced hepatic gluconeogenesis. [1]

In rats treated with metformin, hepatic expression of SEREP-1 mRNAs/protein and activity of ACC were reduced. [2] In metformin treated mice, LKB1 in liver was essential for the ability of metformin to reduce blood glucose [3]. In ASO (Antisense oligonucleotide) knockdown of hepatic mGOD in rats, the phenotype was similar to chronic metformin treatment. It abolished mefromin-induced cytosolic redox state, reduction in plasma glucose concentration and EGP inhibition. [1]

References:
1. Madiraju AK, Erion DM, Rahimi Y et al.  Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.  Nature. 2014 Jun 26;510(7506):542-6.
2. Zhou G, Myers R, Li Y et al.  Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74.
3. Shaw RJ, Lamia KA, Vasquez D et al.  The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005 Dec 9;310(5754):1642-6.

文献引用

1. Yeo SK, Paul R, et al. "Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer." Autophagy. 2018;14(7):1214-1225. PMID:29938573
2. Dong L, Li Y, et al. "Dietary Apostichopus japonicus Alleviates Diabetes Symptoms and Modulates Genes Expression in Kidney Tissues of db/db Mice." J Agric Food Chem. 2018 Jan 2. PMID:29249162

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt165.62
Cas No.1115-70-4
FormulaC4H12ClN5
Solubility≥8.3mg/mL in DMSO
Chemical Name3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride
SDFDownload SDF
Canonical SMILESCN(C)C(=N)N=C(N)N.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

AMPK测定试验

对于AMPK测定,将细胞以1.5×10 6个细胞/孔接种在含有100U / ml青霉素,100μg/ ml链霉素,10%FBS,100nM胰岛素,100nM地塞米松和5μg/ml转铁蛋白的DMEM中处理4小时。然后将细胞在无血清DMEM中培养16小时,随后用所示浓度的对照培养基,5-氨基 - 咪唑甲酰胺核糖苷(AICAR)或Metformin处理1小时或7小时。对照和Metformin(10或20μM)组细胞在DMEM加5%FBS和100nM胰岛素中培养,处理39小时,并且每12小时更换新鲜对照和含Metformin的培养基(最后培养基改变是收获前3小时)。将细胞直接在含有毛地黄皂苷和磷酸酶抑制剂的缓冲液A中裂解,随后用35%饱和度的硫酸铵沉淀。通过测量合成肽底物SAMS(HMRSAMSGLHLVKRR)的磷酸化来测定AMPK活性。

细胞实验 [1]:

细胞系

大鼠原代肝细胞

溶解方法

该化合物在DMSO中的溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

10、20、500μM、2mM; 处理39h;

应用

Metformin在原代肝细胞中激活AMPK。 此外,Metformin(2mM,3小时)刺激骨骼肌中的AMPK活性、与葡萄糖摄取的诱导相关。 二甲双胍(500μM)减少大鼠肝细胞表达SREBP-1。

动物实验:

动物模型

雄性C57BL/6鼠模型

剂量

200 mg / kg、口服、每日两次、共5天; 或250mg / kg、腹膜内注射、持续3天

应用

在metformin治疗的大鼠中乙酰辅酶A羧化酶(ACC)活性降低 [1]。 此外,metformin需要肝脏中的LKB1以降低血糖水平 [2]。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J. and Moller, D. E. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 108, 1167-1174

2Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S. H., Bardeesy, N., Depinho, R. A., Montminy, M. and Cantley, L. C. (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 310, 1642-1646

质量控制

质量控制和MSDS

批次:

化学结构

Metformin HCl

相关生物数据

Metformin HCl

相关生物数据

Metformin HCl