Abstract:
AIMS/HYPOTHESIS:Glomerular mesangial expansion is a characteristic feature of diabetic nephropathy, and the accumulation of AGE in the mesangial lesion has been implicated as one of its potential causes. However, the route for the AGE accumulation in mesangial lesions in diabetic patients is poorly established. METHODS:Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were prepared as model AGE proteins, and their in vivo plasma clearance was examined in mice, and renal uptake by in vitro studies with isolated renal mesangial cells. RESULTS:Both (111)In-GA-BSA and (111)In-MG-BSA were rapidly cleared from the circulation mainly by both the liver and kidney. Immunohistochemical studies with an anti-GA-BSA antibody demonstrated that intravenously injected GA-BSA accumulated in mesangial cells, suggesting that such cells play an important role in the renal clearance of circulating AGE proteins. Binding experiments at 4 degrees C using mesangial cells isolated from mice showed that (125)I-GA-BSA and (125)I-MG-BSA exhibited specific and saturable binding. Upon incubation at 37 degrees C, (125)I-GA-BSA and (125)I-MG-BSA underwent endocytic degradation by these cells. The binding of the ligands to these cells was inhibited by several ligands for scavenger receptors. The endocytic degradation of GA-BSA by mesangial cells from class A scavenger receptor (SR-A) knock-out mice was reduced by 80% when compared with that of wild-type cells. The glomerular accumulation of GA-BSA after its intravenous administration was attenuated in SR-A knock-out mice, as evidenced by immunohistochemical observations. CONCLUSIONS/INTERPRETATION:These results raise the possibility that circulating AGE-modified proteins are subjected to renal clearance by mesangial cells, mainly via SR-A. This pathway may contribute to the pathogenesis of AGE-induced diabetic nephropathy.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Nakajou K,Horiuchi S,Sakai M,Haraguchi N,Tanaka M,Takeya M,Otagiri Mdoi
10.1007/s00125-004-1646-6subject
Has Abstractpub_date
2005-02-01 00:00:00pages
317-27issue
2eissn
0012-186Xissn
1432-0428journal_volume
48pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract::Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between p...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00399934
更新日期:1992-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to examine the association between lifetime breast-feeding and the incidence of type 2 diabetes mellitus in a large population-based cohort study of middle-aged women. METHODS:This was a prospective study of 62,095 middle-aged parous women in Shanghai, China, who had no prior ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0885-8
更新日期:2008-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Post-translational modifications, such as isomerisation of native proteins, may create new antigenic epitopes and play a role in the development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises and repair...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0556-1
更新日期:2007-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would amel...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1444-1
更新日期:2004-07-01 00:00:00
abstract:AIM/HYPOTHESIS:Mitochondria and the endoplasmic reticulum (ER) physically interact by close structural juxtaposition, via the mitochondria-associated ER membrane. Inter-organelle communication between the ER and mitochondria has been shown to regulate energy metabolism and to be central to the modulation of various key...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3704-7
更新日期:2015-10-01 00:00:00
abstract::Most polypeptides originally assigned to a specific organ and a specific effect seem to occur in many different parts of the body, in neurons as well as in endocrine cells. Thus gastrin and insulin, or very similar peptides can be demonstrated in extracts of the vagal nerves and of peripheral somatic nerves. Electrica...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00254501
更新日期:1981-03-01 00:00:00
abstract::We have developed a mouse monoclonal antibody against rat/mouse islet amyloid polypeptide (IAPP). The antibody recognises an epitope in the N-terminal part of the molecule, which is conserved between different species. The antibody immunohistochemically labelled beta cells in normal islets of most different mammalian ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050751
更新日期:1997-07-01 00:00:00
abstract::Highly purified insulins offer the possibility of reducing insulin antibody levels and insulin requirement. Those likely to respond cannot be predicted on clinical grounds and a simple laboratory test is recommended for this purpose. This is based on insulin binding capacity (IBC) of plasma and has been used to follow...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01223271
更新日期:1977-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect o...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0369-2
更新日期:2006-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:We aimed to assess whether persistence of C-peptide secretion is associated with less glucose variability and fewer low-glucose events in adults with type 1 diabetes who use flash monitoring. METHODS:We performed a cross-sectional study of 290 adults attending a university teaching hospital diabetes cl...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05099-3
更新日期:2020-05-01 00:00:00
abstract::Diabetic nephropathy is the main cause of increased mortality and morbidity in IDDM patients. The effect of antihypertensive treatment on the progression of the nephropathy is highly variable. The aim of this study was to evaluate putative predictors of the progression in diabetic nephropathy during long-term antihyp...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050140
更新日期:1994-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2993-y
更新日期:2013-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes. SUBJECTS, MATERIALS AND METHODS:This was a single-centre, randomised, double-blind study in drug-naive patients with type 2 diabetes. Pa...
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-006-0340-2
更新日期:2006-09-01 00:00:00
abstract::The effects of the aldose reductase inhibitor, sorbinil, on symptomatic symmetrical diabetic polyneuropathy were studied during a 6-month period in a double-blind parallel group placebo-controlled trial. Twenty-seven patients received sorbinil and 28 placebo. The patients were assessed by clinical examination, neuroph...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/BF00283137
更新日期:1985-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of the study was to evaluate the relationship between insulin sensitivity, beta cell function and glucose tolerance, and its dependence on variants in the newly identified Type 2 diabetes susceptibility gene, calpain-10 ( CAPN10). METHODS:We studied 203 men of the same age but with varying degr...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1393-8
更新日期:2004-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:The cardiometabolic risk associated with metabolically healthy obesity (MHO) remains the subject of debate. It is unclear whether MHO is a transient condition that affects subclinical atherosclerosis risk. In this study, we aimed to investigate the association of MHO and its transition over time with in...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05116-5
更新日期:2020-07-01 00:00:00
abstract::Two sequential studies of life quality among pancreas transplant recipients are reported. The first study (n = 32) investigated symptoms of neuropathy, enteropathy and retinopathy, along with well-being post successful transplantation. Patients noted improvement in secondary complications, were satisfied with the proc...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00587641
更新日期:1991-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Mitochondrial dysfunction has been postulated to underlie muscular fat accumulation, leading to muscular insulin sensitivity and ultimately type 2 diabetes mellitus. Here we re-interpret previously published data on [(13)C]acetate recovery in breath gas obtained during exercise in type 2 diabetic patien...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-008-1069-x
更新日期:2008-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:The gut hormone glucagon-like peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present study we...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1787-2
更新日期:2005-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes. METHODS:C57/BL6J mice were placed on an HF diet for 3 months and treated with L803-mts for 20...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0552-5
更新日期:2007-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes. METHODS:Liver biopsy samples were obtaine...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1366-y
更新日期:2004-04-01 00:00:00
abstract::Isolated pancreatic islets of normoglycemic sand rats do not respond to 2.5 mM glucose with an enhanced glucagon secretion, which could be observed in normal Wistar rats. Arginine stimulates glucagon release in the presence of 2.5 mM glucose in Wistar rats as well as in sand rats. The secretion pattern is not caused b...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00422820
更新日期:1975-02-01 00:00:00
abstract::We have recently shown that leptin mimicks insulin effects on glucose transport and glycogen synthesis through a phosphatidylinositol-3 (PI) kinase dependent pathway in C2C12 myotubes. The aim of the present study was to identify the signalling path from the leptin receptor to the PI-3 kinase. We stimulated C2C12 myot...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050832
更新日期:1997-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. METHODS:The study was performed within the Hoorn Study, a population-based study of glucose metabolism in indi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2864-6
更新日期:2013-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. MATERIALS AND METHODS:We performed a cross-sectional study of MBL protein concentratio...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0381-6
更新日期:2006-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of the study was to identify surface bio-markers and corresponding antibody tools that can be used for the imaging and immunoisolation of the pancreatic beta cell and its progenitors. This may prove essential to obtain therapeutic grade human beta cells via stem cell differentiation. METHODS:Us...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2295-1
更新日期:2012-01-01 00:00:00
abstract::The insulin-like growth factor I receptor and the activity of its associated tyrosine kinase activity were characterised in wheat germ agglutinin extracts from skeletal muscle biopsies from nine control and ten obese Type 2 (non-insulin-dependent) diabetic subjects, who had marked peripheral in vivo insulin resistance...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00265369
更新日期:1988-12-01 00:00:00
abstract::Developmental changes in the plasma insulin response to milk ingestion have been determined in neonatal lambs fed by bottle and in naturally suckled infant rabbits. In lambs at 4 days of age and older plasma insulin increased within 5 min of suckling and declined again before increasing to a second peak 60 to 120 min ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01219799
更新日期:1979-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF. METHODS:We first examined whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle ce...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-009-1364-1
更新日期:2009-07-01 00:00:00
abstract::Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403907
更新日期:1996-08-01 00:00:00