The Hormetic Effect of Metformin: “Less Is More”?
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In this paper, the effects of MTF on T2DM on the principal target organs, such as liver, gut, adipose tissue, endothelium, heart, and skeletal muscle, were described.Abstract:
Metformin (MTF) is the first-line therapy for type 2 diabetes (T2DM). The euglycemic effect of MTF is due to the inhibition of hepatic glucose production. Literature reports that the principal molecular mechanism of MTF is the activation of 5'-AMP-activated protein kinase (AMPK) due to the decrement of ATP intracellular content consequent to the inhibition of Complex I, although this effect is obtained only at millimolar concentrations. Conversely, micromolar MTF seems to activate the mitochondrial electron transport chain, increasing ATP production and limiting oxidative stress. This evidence sustains the idea that MTF exerts a hormetic effect based on its concentration in the target tissue. Therefore, in this review we describe the effects of MTF on T2DM on the principal target organs, such as liver, gut, adipose tissue, endothelium, heart, and skeletal muscle. In particular, data indicate that all organs, except the gut, accumulate MTF in the micromolar range when administered in therapeutic doses, unmasking molecular mechanisms that do not depend on Complex I inhibition.read more
Citations
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References
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Journal ArticleDOI
Adipose Tissue as an Endocrine Organ
Erin E. Kershaw,Jeffrey S. Flier +1 more
TL;DR: An overview of the endocrine functions of adipose tissue can be found in this paper, where the authors highlight the adverse metabolic consequences of both adipose excess and deficiency, and propose a more rational therapy for these increasingly prevalent disorders.
Journal ArticleDOI
IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.
Katherine Ogurtsova,J. D. da Rocha Fernandes,Yadi Huang,Ute Linnenkamp,Leonor Guariguata,Nam H. Cho,Nam H. Cho,David Cavan,Jonathan E. Shaw,Lydia Makaroff,Lydia Makaroff +10 more
TL;DR: Diabetes prevalence, deaths attributable to diabetes, and health expenditure due to diabetes continue to rise across the globe with important social, financial and health system implications.
Journal ArticleDOI
Brown Adipose Tissue: Function and Physiological Significance
Barbara Cannon,Jan Nedergaard +1 more
TL;DR: The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
Journal ArticleDOI
A metagenome-wide association study of gut microbiota in type 2 diabetes
Junjie Qin,Yingrui Li,Zhiming Cai,Shenghui Li,Jianfeng Zhu,Fan Zhang,Suisha Liang,Wenwei Zhang,Yuanlin Guan,Dongqian Shen,Yangqing Peng,Dongya Zhang,Zhuye Jie,Wenxian Wu,Youwen Qin,Wenbin Xue,Junhua Li,Lingchuan Han,Donghui Lu,Peixian Wu,Yali Dai,Xiaojuan Sun,Zesong Li,Aifa Tang,Shilong Zhong,Xiaoping Li,Weineng Chen,Ran Xu,Mingbang Wang,Qiang Feng,Meihua Gong,Jing Yu,Yanyan Zhang,Ming Zhang,Torben Hansen,Gaston Sanchez,Jeroen Raes,Gwen Falony,Shujiro Okuda,Mathieu Almeida,Emmanuelle Le-chatelier,Pierre Renault,Nicolas Pons,Jean-Michel Batto,Zhaoxi Zhang,Hua Chen,Ruifu Yang,Wei-Mou Zheng,Songgang Li,Huanming Yang,Jian Wang,S. Dusko Ehrlich,Rasmus Nielsen,Oluf Pedersen,Oluf Pedersen,Karsten Kristiansen,Jun Wang +56 more
TL;DR: MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance.
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TL;DR: Athrosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS.