Abstract:
:Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. CKD raised mRNAs of inflammatory cytokines in muscles and there was a 5.2-fold increase in signal regulatory protein-α (SIRP-α), a transmembrane glycoprotein principally present in muscle membranes. By immunoprecipitation we found it interacts with the insulin receptor and insulin receptor substrate-1 (IRS-1). Treatment of myotubes with a mixture of inflammatory cytokines showed that SIRP-α expression was increased by a NF-κB-dependent pathway. Blockade of NF-κB using a small-molecule chemical inhibitor or a dominant-negative IKKβ reduced cytokine-induced SIRP-α expression. The overexpression of SIRP-α in myotubes impaired insulin signaling and raised proteolysis while SIRP-α knockdown with siRNAs in skeletal muscle cells increased tyrosine phosphorylation of the insulin receptor and IRS-1 despite inclusion of cytokines. This led to increased p-Akt and suppression of protein degradation. Thus, SIRP-α is part of a novel mechanism for inflammation-mediated insulin resistance in muscle. In catabolic conditions with impaired insulin signaling, targeting SIRP-α may improve insulin sensitivity and prevent muscle atrophy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Thomas SS,Dong Y,Zhang L,Mitch WEdoi
10.1038/ki.2013.97subject
Has Abstractpub_date
2013-08-01 00:00:00pages
308-16issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55975-9journal_volume
84pub_type
杂志文章abstract::Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.457
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Knowledge of the long-term renal prognosis of diarrhea associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. However, estimates of long-term risk are highly variable, with previous studies not using a healthy control group. METHODS:A municipal water system in the smal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00225.x
更新日期:2005-04-01 00:00:00
abstract::Calcitonin secretion is stimulated by acute hypercalcemia. Furthermore, in the rat, the calcemic response to parathyroid hormone (PTH) is decreased by calcitonin stimulation. However, in renal failure, it is not known if an increase in the serum calcium concentration within the physiologic range of serum calcium stimu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.263
更新日期:1991-10-01 00:00:00
abstract::Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001727
更新日期:2006-09-01 00:00:00
abstract::Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.67
更新日期:2011-07-01 00:00:00
abstract::Urinary microvesicles, such as 40-100 nm exosomes and 100-1000 nm microparticles, contain many proteins that may serve as biomarkers of renal disease. Microvesicles have been isolated by ultracentrifugation or nanomembrane ultrafiltration from normal urine; however, little is known about the efficiency of these method...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.262
更新日期:2010-10-01 00:00:00
abstract::Urinary exosomes have received considerable attention as a potential biomarker source for the diagnosis of renal diseases. Notwithstanding, their use in protein biomarker research is hampered by the lack of efficient methods for vesicle isolation, lysis, and protein quantification. Here we report an improved ultracent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.25
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:To chart the epidemiology of primary glomerular disease by means of a prospective regional study in the southern part of The Netherlands. METHODS:Experienced renal technicians collected renal biopsies, blood, and 24-hour urine samples at the bed site in each of the participating hospitals. The material was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00835.x
更新日期:2004-09-01 00:00:00
abstract::The involvement of cysteinyl leukotrienes (LT) in the etiology of glomerulonephritis (GN) was investigated in a rat model of nephrotoxic serum nephritis in which renal function, morphology, LTC4 synthase activity and urinary cysteinyl LT excretion were monitored over seven days. Significant alterations in renal functi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.401
更新日期:1994-11-01 00:00:00
abstract::This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled,...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.2011.195
更新日期:2011-10-01 00:00:00
abstract::We report the stepwise application of the RIFLE classification in 155,624 admissions in the UK Intensive Care National Audit & Research Centre Case Mix Programme database. The assumptions required to define RIFLE and their relationship with renal replacement therapy (RRT) and ICU mortality were assessed. Previous repo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.70
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00203.x
更新日期:2000-08-01 00:00:00
abstract::A model of glomerular dynamics has been developed by using network thermodynamics and the SPICE 2 computer program to further explore the determinants of glomerular filtration. The model is designed to be holistic and self-adjusting, taking cognizance of and permitting quantitation of the secondary alterations in indi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.27
更新日期:1981-02-01 00:00:00
abstract::We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized t...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2010.352
更新日期:2011-01-01 00:00:00
abstract::Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.376
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND:Endotoxin is an important factor in the development of acute renal failure related to infection and in acceleration of chronic nephritis. Lipopolysaccharide (LPS; the major component of endotoxin) is one of the most potent triggers for renal cells to produce monocyte chemoattractant protein-1 (MCP-1), a key ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00051.x
更新日期:2000-05-01 00:00:00
abstract::Because of differences in case-mix across states, state-level case-mix-adjusted end-stage renal disease (ESRD) incident rates are reported in each United States Renal Data System Annual Data Report to make the across-state comparisons valid. The adjusted rates were estimated by the direct adjustment method, a widely u...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000299
更新日期:2006-04-01 00:00:00
abstract::Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously, in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscle protein synthesis. The present study is the first to ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.472
更新日期:1994-12-01 00:00:00
abstract::Transgenic rats [TGR; strain name TGR(mRen2)27] harboring the mouse Ren-2 renin gene have been recently generated as a model for the study of primary hypertension that offers the advantage of a clearly-defined genetic alteration. Expression of the mouse Ren-2 gene causes severe hypertension (200 to 260 mm Hg) which is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.4
更新日期:1992-01-01 00:00:00
abstract::Arguably, no cell biology related to the loss of renal function is more debated than the ontogeny of fibrosis in the kidney. Recent studies suggest that the fibroblasts depositing most of the excess extracellular matrix in diseased kidneys derive from epithelial cells versus pericytes resident within the kidney. Reich...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.107
更新日期:2013-07-01 00:00:00
abstract::IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with l...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.466
更新日期:2011-03-01 00:00:00
abstract::Kidney transplant patients receiving phenytoin or phenobarbital may have decreased graft survival. These drugs have been shown to enhance the metabolism of glucocorticoids. We determined the disposition of total and unbound prednisolone in six stable kidney transplant patients receiving prednisone for immunosuppressio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.17
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00071.x
更新日期:2003-07-01 00:00:00
abstract::International clinical practice guidelines for the management of anemia in chronic kidney disease suggest target hemoglobin levels ≤ 11.5 g/dl (115 g/l), with individualized consideration of slightly higher hemoglobin targets to improve quality of life. An updated meta-analysis of randomized trials demonstrates no sig...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.03.001
更新日期:2016-05-01 00:00:00
abstract::Peptides representing potential antigenic regions of the NC-1 and 7-S domains of the human alpha 1 and alpha 2, and bovine alpha 3 chains of type IV collagen were synthesized either chemically or by the recombinant DNA technique and tested by ELISA using antibodies raised in rabbits against the whole type IV collagen ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.16
更新日期:1993-01-01 00:00:00
abstract::Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.359
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND:Peritonitis in peritoneal dialysis patients is accompanied by an enhanced migration of neutrophils (PMNs) and increased protein loss into the peritoneal cavity; however, the role of PMNs in governing increased protein loss during peritonitis associated with peritoneal dialysis is unknown. METHODS:We determi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00019.x
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:Patients initiating dialysis after a failed kidney transplant are a subgroup of chronic kidney disease (CKD) patients who have not been characterized. Exposure to immunosuppressive medications differentiates these patients from the general incident end-stage renal disease (ESRD) population. METHODS:Data fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00373.x
更新日期:2002-06-01 00:00:00
abstract::Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase associated with numerous aspects of health and physiology. Overexpression of SIRT6 has emerged as a protector in cardiac tissues against pathologic cardiac hypertrophy. However, the mechanism of this protective effect is not fully understood. Here, both in vivo and in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.10.021
更新日期:2018-04-01 00:00:00
abstract::Acute kidney injury (AKI) is a critical condition with a mortality rate as high as 50% and significantly contributes to the burden of end-stage renal disease (ESRD) requiring renal replacement therapy. The incidence and prognosis of AKI have been shown to vary with patient age, with younger individuals being more resi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.394
更新日期:2013-03-01 00:00:00