Uric acid transport and disease.
Alexander So,Bernard Thorens +1 more
TLDR
The biology of urate metabolism and its role in disease is discussed and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development are identified.Abstract:
Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.read more
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
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TL;DR: It is established that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity, and that the NlrP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.
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The SLC2 (GLUT) family of membrane transporters.
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Global epidemiology of gout: prevalence, incidence and risk factors
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References
More filters
Journal ArticleDOI
Inflammation and metabolic disorders
TL;DR: Dysfunction of the immune response and metabolic regulation interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease.
Journal ArticleDOI
Gout-associated uric acid crystals activate the NALP3 inflammasome
TL;DR: It is shown that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18 in mice deficient in the IL-1β receptor.
Journal ArticleDOI
Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.
TL;DR: It is shown that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects ERYthrocytes from peroxidative damage leading to lysis.
Journal ArticleDOI
Uric acid and cardiovascular risk.
TL;DR: This review summarizes relevant studies concerning uric acid and possible links to hypertension, renal disease, and cardiovascular disease and presents current evidence.
Journal ArticleDOI
Molecular identification of a renal urate anion exchanger that regulates blood urate levels.
Atsushi Enomoto,Hiroaki Kimura,Hiroaki Kimura,Arthit Chairoungdua,Yasuhiro Shigeta,Yasuhiro Shigeta,Promsuk Jutabha,Seok Ho Cha,Makoto Hosoyamada,Michio Takeda,Takashi Sekine,Takashi Igarashi,Hirotaka Matsuo,Hirotaka Matsuo,Yuichi Kikuchi,Takashi Oda,Kimiyoshi Ichida,Tatsuo Hosoya,Kaoru Shimokata,Toshimitsu Niwa,Yoshikatsu Kanai,Hitoshi Endou +21 more
TL;DR: This work identifies the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate–anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricOSuric agents (which affect excretion of uric acid).
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