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二甲双胍:超越糖尿病的潜在机制和治疗效用的综述。

Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.

机构信息

Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India.

Department of Medical Surgical Nursing, Shri Anand Institute of Nursing, Rajkot, Gujarat, 360005, India.

出版信息

Drug Des Devel Ther. 2023 Jun 26;17:1907-1932. doi: 10.2147/DDDT.S409373. eCollection 2023.

DOI:10.2147/DDDT.S409373
PMID:37397787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10312383/
Abstract

Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin's neuroprotective role in Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

摘要

二甲双胍被指定为 2 型糖尿病管理中最重要的一线治疗药物之一。作为一种主要的抗高血糖药物,二甲双胍对各种系统和过程也具有多种多效性作用。它主要通过在细胞中激活 AMPK(腺苷单磷酸激活蛋白激酶)并减少肝脏的葡萄糖输出来发挥作用。它还可以减少内皮细胞中晚期糖基化终产物和活性氧物质的产生,除了调节心肌细胞中的葡萄糖和脂质代谢外,还可以最大程度地降低心血管风险。其对恶性细胞的抗癌、抗增殖和诱导凋亡作用可能有助于预防乳腺癌、肾脏、大脑、卵巢、肺和子宫内膜等器官的恶性肿瘤。临床前研究还表明,二甲双胍在帕金森病、阿尔茨海默病、多发性硬化症和亨廷顿病中的神经保护作用有一定的证据。二甲双胍通过多种细胞内信号转导途径发挥其多效性作用,其在大多数情况下的确切机制仍有待明确。本文广泛综述了二甲双胍的治疗益处及其作用机制的细节,包括在糖尿病、糖尿病前期、肥胖症、多囊卵巢综合征、HIV 代谢紊乱、各种癌症和衰老等多种情况下的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/fed569e7c60d/DDDT-17-1907-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/206d3dd80f37/DDDT-17-1907-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/28aa99250e51/DDDT-17-1907-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/fed569e7c60d/DDDT-17-1907-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/206d3dd80f37/DDDT-17-1907-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/28aa99250e51/DDDT-17-1907-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df02/10312383/fed569e7c60d/DDDT-17-1907-g0003.jpg

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