Inflammasomes: mechanism of action, role in disease, and therapeutics

Nature Medicine, Journal Year: 2015, Volume and Issue: 21(7), P. 677 - 687

Published: June 29, 2015

Language: Английский

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Pathophysiology of Type 2 Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6275 - 6275

Published: Aug. 30, 2020

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination two primary factors: defective insulin secretion pancreatic β-cells and inability insulin-sensitive tissues to respond appropriately insulin. Because release activity are essential processes for glucose homeostasis, molecular mechanisms involved in synthesis insulin, as well its detection tightly regulated. Defects any these can lead imbalance responsible development disease. This review analyzes key aspects T2DM, pathways implicated metabolism leading T2DM resistance. For that purpose, we summarize data gathered up until now, focusing especially on synthesis, release, sensing downstream effects individual organs. The also covers pathological conditions perpetuating such nutritional factors, physical activity, gut dysbiosis memory. Additionally, because associated with accelerated atherosclerosis development, here some link resistance (IR) cardiovascular risk important complications T2DM.

Language: Английский

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Molecular mechanisms regulating NLRP3 inflammasome activation

Cellular and Molecular Immunology, Journal Year: 2015, Volume and Issue: 13(2), P. 148 - 159

Published: Nov. 9, 2015

Language: Английский

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Adipose tissue inflammation and metabolic dysfunction in obesity

AJP Cell Physiology, Journal Year: 2020, Volume and Issue: 320(3), P. C375 - C391

Published: Dec. 23, 2020

Several lines of preclinical and clinical research have confirmed that chronic low-grade inflammation adipose tissue is mechanistically linked to metabolic disease organ complications in the overweight obese organism. Despite this widely paradigm, numerous open questions knowledge gaps remain be investigated. This mainly due intricately intertwined cross-talk various pro- anti-inflammatory signaling cascades involved immune response expanding depots, particularly visceral tissue. Adipose initiated sustained over time by dysfunctional adipocytes secrete inflammatory adipokines infiltration bone marrow-derived cells signal via production cytokines chemokines. its nature, negatively impacts remote function, a phenomenon considered causative obesity. The aim review broadly present an overview highlighting most recent reports scientific literature summarizing our overall understanding field. We also discuss key endogenous mediators analyze their mechanistic role(s) pathogenesis treatment inflammation. In doing so, we hope stimulate studies uncover novel physiological, cellular, molecular targets for

Language: Английский

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Autophagy—a key player in cellular and body metabolism

Nature Reviews Endocrinology, Journal Year: 2014, Volume and Issue: 10(6), P. 322 - 337

Published: March 25, 2014

Language: Английский

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The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(5), P. 1835 - 1835

Published: March 6, 2020

Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share common main feature chronic hyperglycemia results from defects insulin secretion, action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, carbohydrates. Atherosclerosis develops as result multistep process ultimately leading cardiovascular disease associated with high morbidity mortality. Alteration lipid risk factor characteristic atherosclerosis. Possible links between the two depending on altered pathways have been investigated numerous studies. It was shown both types diabetes can actually induce atherosclerosis development further accelerate progression. Elevated glucose level, dyslipidemia, other alterations accompany are tightly involved pathogenesis at almost every step atherogenic process. Chronic inflammation currently considered one key factors present starting earliest stages pathology initiation. may also be regarded possible mellitus. However, data available so far do not allow for developing effective anti-inflammatory therapeutic strategies would stop atherosclerotic lesion progression reduction. In this review, we summarize aspects possibly affect relationship inflammation. We discuss established pathophysiological features link mellitus, such oxidative stress, protein kinase signaling, role certain miRNA epigenetic modifications.

Language: Английский

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AMPK, insulin resistance, and the metabolic syndrome

Journal of Clinical Investigation, Journal Year: 2013, Volume and Issue: 123(7), P. 2764 - 2772

Published: June 30, 2013

Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as central adiposity, dyslipidemia, a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, certain cancers. Regular exercise calorie restriction have long been known increase insulin sensitivity decrease prevalence these disorders. The subsequent identification AMP-activated protein kinase (AMPK) its activation by fuel deprivation led studies effects AMPK on both IR syndrome–related diseases. In this review, we evaluate body literature, with special emphasis hypothesis that dysregulation is pathogenic factor for disorders in humans target their prevention therapy.

Language: Английский

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Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 29, 2020

Obesity is one of the major health burdens 21st century as it contributes to growing prevalence its related comorbidities, including insulin resistance and type 2 diabetes. Overwhelming evidence suggests a critical role for overnutrition in development low-grade inflammation. Specifically, chronic inflammation adipose tissue considered crucial risk factor diabetes obese individuals. The triggers are still poorly defined. However, obesity-induced expansion provides plethora intrinsic signals (e.g., adipocyte death, hypoxia, mechanical stress) capable initiating inflammatory response. Immune dysregulation subjects results characterized by increased infiltration activation innate adaptive immune cells. Macrophages most abundant cells infiltrating accumulating into individuals; they constitute up 40% all obesity. In obesity, macrophages polarized pro-inflammatory M1 secrete many cytokines impairing signaling; therefore, promoting progression resistance. Besides macrophages, other dendritic cells, mast neutrophils, B T cells) reside during playing key association inflammation, metabolic diseases makes pathways an appealing target treatment obesity-related complications. this review, we summarize molecular mechanisms responsible toward obesity-associated comorbidities highlight current therapeutic strategies.

Language: Английский

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Targeting inflammation in the treatment of type 2 diabetes: time to start

Nature Reviews Drug Discovery, Journal Year: 2014, Volume and Issue: 13(6), P. 465 - 476

Published: May 23, 2014

Language: Английский

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Macrophage polarization in pathology

Cellular and Molecular Life Sciences, Journal Year: 2015, Volume and Issue: 72(21), P. 4111 - 4126

Published: July 25, 2015

Language: Английский

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