Immunometabolism in the development of rheumatoid arthritis DOI
Cornelia M. Weyand, Jörg J. Goronzy

Immunological Reviews, Год журнала: 2020, Номер 294(1), С. 177 - 187

Опубликована: Янв. 27, 2020

Abstract In rheumatoid arthritis (RA), breakdown of self‐tolerance and onset clinical disease are separated in time space, supporting a multi‐hit model which emergence autoreactive T cells is pinnacle pathogenic event. Determining factors cell differentiation survival include antigen recognition, but also the metabolic machinery that provides energy biosynthetic molecules for building. Studies patients with RA have yielded disease‐specific signature, enables naive CD4 to differentiate into pro‐inflammatory helper prone invade tissue elicit inflammation through immunogenic death. A typifying property shunting glucose away from glycolytic mitochondrial processing toward pentose phosphate pathway, favoring anabolic over catabolic reactions. Key defects been localized mitochondria lysosome; including instability DNA due lack repair nuclease MRE11A inefficient lysosomal tethering AMPK deficiency N‐myristoyltransferase 1 (NMT1). The molecular taxonomy metabolically reprogrammed includes enzymes (glucose‐6‐phosphate dehydrogenase, phosphofructokinase), (MRE11A, ATM), regulators protein trafficking (NMT1), membrane adapter TSK5. As mechanisms determining abnormal behavior unraveled, opportunities will emerge interject autoimmune by targeting their checkpoints.

Язык: Английский

Insulin Resistance: From Mechanisms to Therapeutic Strategies DOI Creative Commons
Shin-Hae Lee,

Shi‐Young Park,

Cheol Soo Choi

и другие.

Diabetes & Metabolism Journal, Год журнала: 2021, Номер 46(1), С. 15 - 37

Опубликована: Дек. 30, 2021

Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and defined as a state reduced responsiveness insulin-targeting tissues to physiological levels insulin. Although underlying mechanism insulin not fully understood, several credible theories have been proposed. In this review, we summarize functions in glucose metabolism typical describe mechanisms proposed underlie resistance, that is, ectopic lipid accumulation liver skeletal muscle, endoplasmic reticulum stress, inflammation. addition, suggest potential therapeutic strategies for addressing resistance.

Язык: Английский

Процитировано

523
GDF15 mediates the effects of metformin on body weight and energy balance DOI
Anthony P. Coll, Michael Chen, Pranali Taskar

и другие.

Nature, Год журнала: 2019, Номер 578(7795), С. 444 - 448

Опубликована: Дек. 25, 2019

Язык: Английский

Процитировано

451
Low-dose metformin targets the lysosomal AMPK pathway through PEN2 DOI Creative Commons
Teng Ma, Xiao Tian, Baoding Zhang

и другие.

Nature, Год журнала: 2022, Номер 603(7899), С. 159 - 165

Опубликована: Фев. 23, 2022

Abstract Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects 1–4 . For clinical doses of metformin, AMP-activated protein kinase (AMPK) a major role in its mechanism action 4,5 ; however, direct molecular target metformin remains unknown. Here we show that clinically relevant concentrations inhibit lysosomal proton pump v-ATPase, which is central node for AMPK activation following glucose starvation 6 We synthesize photoactive probe identify PEN2, subunit γ-secretase 7 , binding partner with dissociation constant at micromolar levels. Metformin-bound PEN2 forms complex ATP6AP1, v-ATPase 8 leads to inhibition without on cellular AMP Knockout or re-introduction mutant does not bind ATP6AP1 blunts activation. In vivo, liver-specific knockout Pen2 abolishes metformin-mediated reduction hepatic fat content, whereas intestine-specific impairs glucose-lowering effects. Furthermore, knockdown pen-2 Caenorhabditis elegans abrogates metformin-induced extension lifespan. Together, these findings reveal binds initiates signalling route intersects, through glucose-sensing pathway This ensures exerts therapeutic patients substantial adverse

Язык: Английский

Процитировано

369
Metformin: update on mechanisms of action and repurposing potential DOI Open Access
Marc Foretz, Bruno Guigas, Benoı̂t Viollet

и другие.

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(8), С. 460 - 476

Опубликована: Май 2, 2023

Язык: Английский

Процитировано

326
GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease DOI
Dongdong Wang, Emily A. Day, Logan K. Townsend

и другие.

Nature Reviews Endocrinology, Год журнала: 2021, Номер 17(10), С. 592 - 607

Опубликована: Авг. 11, 2021

Язык: Английский

Процитировано

312
The molecular mechanisms of copper metabolism and its roles in human diseases DOI
Ji Chen,

Yunhui Jiang,

Shi H

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2020, Номер 472(10), С. 1415 - 1429

Опубликована: Июнь 7, 2020

Язык: Английский

Процитировано

307
Targeting cancer-promoting inflammation — have anti-inflammatory therapies come of age? DOI
Jiajie Hou, Michael Karin, Beicheng Sun

и другие.

Nature Reviews Clinical Oncology, Год журнала: 2021, Номер 18(5), С. 261 - 279

Опубликована: Янв. 19, 2021

Язык: Английский

Процитировано

261
Diabetic vascular diseases: molecular mechanisms and therapeutic strategies DOI Creative Commons

Yiwen Li,

Yanfei Liu, Shiwei Liu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Апрель 10, 2023

Abstract Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on single vascular complication are no longer suitable for the long-term management patients with diabetes. Diabetic panvascular disease (DPD) is clinical syndrome in which vessels various sizes, including macrovessels microvessels cardiac, cerebral, renal, ophthalmic, peripheral systems diabetes, develop atherosclerosis as common pathology. Pathological manifestations DPDs usually manifest macrovascular atherosclerosis, well microvascular endothelial function impairment, basement membrane thickening, microthrombosis. Cardiac, microangiopathy coexist microangiopathy, while renal retinal predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, risk-predictive relationships diseases. Aggressive glycemic control combined early comprehensive intervention key prevention treatment. In addition widely recommended metformin, glucagon-like peptide-1 agonist, sodium-glucose cotransporter-2 inhibitors, latest aldose reductase peroxisome proliferator-activated receptor-γ agonizts, glucokinases mitochondrial energy modulators, etc. under active development. proposed obtain more systematic care requires center focusing This would leverage advantages cross-disciplinary approach achieve better integration pathogenesis therapeutic evidence. Such strategy confer benefits promote development DPD discipline.

Язык: Английский

Процитировано

250
Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments DOI Creative Commons
Mina Wang, Yan Tan, Yifan Shi

и другие.

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Авг. 25, 2020

Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging general obesity. The pathogenesis of sarcopenic includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, hormonal changes. Nevertheless, there major forms to cause diabetes: impaired secretion action. Furthermore, the individual diagnosis sarcopenia should be combined adequately define Also, fasting plasma glucose test (FPG), two-hour oral tolerance (OGTT), glycated hemoglobin (A1C), random coupled with symptoms. Healthy diet activity beneficial diabetes, but only recommended drugs for diabetes. This review consolidates discusses latest research in pathogenesis, diagnosis, treatments

Язык: Английский

Процитировано

167
Treatments for NAFLD: State of Art DOI Open Access
Alessandro Mantovani, Andrea Dalbeni

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2350 - 2350

Опубликована: Фев. 26, 2021

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults general population and up 70% patients with type 2 diabetes (T2DM). Despite current knowledge epidemiology, pathogenesis, natural history NAFLD, no specific pharmacological therapies are until now approved for this strategies have been proposed manage it. They include: (a) lifestyle change order promote weight loss by diet physical activity, (b) control main cardiometabolic risk factors, (c) correction all modifiable factors leading development progression advanced forms (d) prevention hepatic extra-hepatic complications. In last decade, several potential agents widely investigated treatment NAFLD its forms—shedding some light but casting few shadows. include glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants vitamin E), statins or other lipid lowering agents, bile non-bile acid farnesoid X activated (FXR) others. This narrative review discusses detail different available approaches prevent treat forms.

Язык: Английский

Процитировано

161