Abstract:
:Mitochondrial injury is uniformly observed in several murine models as well as in individuals with diabetic kidney disease (DKD). Although emerging evidence has highlighted the role of key transcriptional regulators in mitochondrial biogenesis, little is known about the regulation of mitochondrial cytochrome c oxidase assembly in the podocyte under diabetic conditions. We recently reported a critical role of the zinc finger Krüppel-like factor 6 (KLF6) in maintaining mitochondrial function and preventing apoptosis in a proteinuric murine model. In this study, we report that podocyte-specific knockdown of Klf6 increased the susceptibility to streptozotocin-induced DKD in the resistant C57BL/6 mouse strain. We observed that the loss of KLF6 in podocytes reduced the expression of synthesis of cytochrome c oxidase 2 with resultant increased mitochondrial injury, leading to activation of the intrinsic apoptotic pathway under diabetic conditions. Conversely, mitochondrial injury and apoptosis were significantly attenuated with overexpression of KLF6 in cultured human podocytes under hyperglycemic conditions. Finally, we observed a significant reduction in glomerular and podocyte-specific expression of KLF6 in human kidney biopsies with progression of DKD. Collectively, these data suggest that podocyte-specific KLF6 is critical to preventing mitochondrial injury and apoptosis under diabetic conditions.
journal_name
Diabetesjournal_title
Diabetesauthors
Horne SJ,Vasquez JM,Guo Y,Ly V,Piret SE,Leonardo AR,Ling J,Revelo MP,Bogenhagen D,Yang VW,He JC,Mallipattu SKdoi
10.2337/db17-0958subject
Has Abstractpub_date
2018-11-01 00:00:00pages
2420-2433issue
11eissn
0012-1797issn
1939-327Xpii
db17-0958journal_volume
67pub_type
杂志文章相关文献
DIABETES文献大全abstract::There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1423
更新日期:2016-09-01 00:00:00
abstract::Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0630
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0839
更新日期:2010-03-01 00:00:00
abstract::Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to direct changes in heart muscle function independent of vascular disease. An important contributor to contractile dysfunction in the diabetic state is an impaired sarcoplasmic reticulum (SR) function, leading to disturbed intracellular cal...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.1166
更新日期:2002-04-01 00:00:00
abstract::Retinal neovascularization is observed in progression of diabetic retinopathy. New vessels grow into the vitreous cavity in proliferative diabetic retinopathy, resulting in traction retinal detachment and vitreous hemorrhage. To overcome the catastrophic visual loss due to these complications, efforts have been focuse...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1541
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVE:To investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND METHODS:We monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of auto...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0498
更新日期:2010-04-01 00:00:00
abstract::In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and seve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0284
更新日期:2016-08-01 00:00:00
abstract::Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4+Foxp3+ regulatory T cells (Tregs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded Tregs in T1D and solid-organ transp...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0061
更新日期:2020-02-01 00:00:00
abstract::Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.5.420
更新日期:1976-05-01 00:00:00
abstract::Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby, the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0547
更新日期:2017-01-01 00:00:00
abstract::Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.4.460
更新日期:1990-04-01 00:00:00
abstract::The aim of the present study was to evaluate and cor-relate islet to brown and white adipose tissue (WAT) blood perfusion in one obese rat and one nonobese rat with type 2 diabetes (obese Zucker [OZ] and GK rats, respectively). We measured blood perfusion with a microsphere technique in anesthetized animals and subseq...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.9.2620
更新日期:2005-09-01 00:00:00
abstract::Diabetic hearts exhibit decreased responsiveness to stimulation by beta-adrenoreceptor (beta-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of beta-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreas...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2.455
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESI...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1191
更新日期:2010-04-01 00:00:00
abstract::Widely held theories of the pathogenesis of obesity-associated NIDDM have implicated apparently incompatible events as seminal: 1) insulin resistance in muscle, 2) abnormal secretion of insulin, and 3) increases in intra-abdominal fat. Altered circulating or tissue lipids are characteristic features of obesity and NID...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.45.3.273
更新日期:1996-03-01 00:00:00
abstract::We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2676
更新日期:2004-10-01 00:00:00
abstract::Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. The recent escalation of obesity in affluent cou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1273
更新日期:2013-07-01 00:00:00
abstract::Both genetic and nongenetic factors contribute to the development of type 1 diabetes. Many investigations, including prospective studies of high-risk children, have implicated virus infections as predisposing environmental agents. We previously reported that basal activity of the key antiviral enzyme 2'5'-oligoadenyla...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1588
更新日期:2005-05-01 00:00:00
abstract::The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte globulin and etanercept induction, islet culture, heparinization, and intensive insulin therapy with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engraf...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1802
更新日期:2013-08-01 00:00:00
abstract::ATP is known to be coreleased with insulin from pancreatic beta-cells. To monitor insulin secretion from single beta-cells, a single beta-cell was surrounded in culture by Fura 2-loaded calf pulmonary artery endothelium (CPAE) cells, which can detect the ATP. CPAE cells did not respond with an elevation in cytoplasmic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.10.1213
更新日期:1995-10-01 00:00:00
abstract::Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determine whether FA uptake and disposal are altered in insulin-resistant muscle, we measured palmitate uptake, oxidation, and incorporation into di- and triglycerides in isolat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.6.1389
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0121
更新日期:2011-08-01 00:00:00
abstract::The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1477
更新日期:2017-05-01 00:00:00
abstract::The identity of the cells responsible for beta-cell destruction in type I (insulin-dependent) diabetes is still uncertain. L3T4+ T-lymphocytes have a role in the initiation of insulitis and in damaging transplanted allogeneic islets in nonobese diabetic (NOD) mice. The role of L3T4+ T-lymphocytes in destruction of bet...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.8.1108
更新日期:1988-08-01 00:00:00
abstract::Although non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in insulin action, the molecular basis of this resistance is unknown. We studied fibroblasts from a markedly insulin-resistant patient with NIDDM but without acanthosis nigricans. Her fibroblasts were resistant to insulin when alpha-am...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.2.295
更新日期:1991-02-01 00:00:00
abstract::Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.3.893
更新日期:2005-03-01 00:00:00
abstract::Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., r...
journal_title:Diabetes
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract::AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking. In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle. In addition, we compared the effect of physiological hyperinsulinemia on AS160 phosphorylation...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.6.1692
更新日期:2005-06-01 00:00:00
abstract::Pancreatic β-cells play a pivotal role in maintaining normoglycemia. Recent studies have revealed that the β-cell is not a homogeneous cell population but, rather, is heterogeneous in a number of properties such as electrical activity, gene expression, and cell surface markers. Identification of specific β-cell subpop...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0072
更新日期:2019-06-01 00:00:00
abstract::Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.1.6
更新日期:1986-01-01 00:00:00