Abstract:
:Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and influence ECM synthesis in experimental diabetes. To test our hypothesis, we initially studied the dynamics of glomerular macrophage recruitment in streptozotocin-induced diabetic rats at days 1, 2, 4, 8, 15, and 30 by using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated glomeruli and immunohistochemistry and morphometry. We then assessed the role of macrophages on the basis of the pharmacological modulation of their recruitment by insulin or ACE inhibitor treatments and by X-irradiation-induced macrophage depletion at days 8 and 30. Macrophages were recruited within the glomeruli at the very early phase of hyperglycemia by using RT-PCR CD14 detection from day 2 and by using ED1 immunohistochemistry from day 8. This glomerular macrophage infiltration was associated with an increase in alpha1-chain type IV collagen mRNA. In parallel, the diabetic glomeruli became hypertrophic with an increase in the mesangial area. Macrophage recruitment was preceded by or associated with an increased glomerular expression of vascular cell adhesion molecule 1, intracellular adhesion molecule 1, and monocyte chemoattractant protein 1, which contributes to monocyte diapedesis. Glomerular interleukin-1beta mRNA synthesis was also enhanced as early as day 1 and could be involved in the increase in ECM and adhesion molecule gene expressions. Insulin treatment and irradiation-induced macrophage depletion completely prevented the glomerular macrophage recruitment and decreased alpha1-chain type IV collagen mRNA and mesangial area in diabetic rats, whereas ACE inhibitor treatment had an incomplete effect. It can be concluded that in the streptozotocin model, hyperglycemia is followed by an early macrophage recruitment that contributes to the molecular and structural events that could lead to glomerulosclerosis. Therefore, besides direct stimulation of mesangial cells by hyperglycemia, macrophages recruited in the glomeruli during the early phase of hyperglycemia could secondarily act on mesangial cells.
journal_name
Diabetesjournal_title
Diabetesauthors
Sassy-Prigent C,Heudes D,Mandet C,Bélair MF,Michel O,Perdereau B,Bariéty J,Bruneval Pdoi
10.2337/diabetes.49.3.466subject
Has Abstractpub_date
2000-03-01 00:00:00pages
466-75issue
3eissn
0012-1797issn
1939-327Xjournal_volume
49pub_type
杂志文章相关文献
DIABETES文献大全abstract::The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1069
更新日期:1992-09-01 00:00:00
abstract::A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasm...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.5.500
更新日期:1977-05-01 00:00:00
abstract::Duct-occluded segmental-pancreas transplants develop progressive fibrotic atrophy, even though endocrine function seems to be unaffected. To determine end-stage size of the graft and to evaluate magnetic resonance imaging (MRI) and computed tomography (CT), these imaging techniques were applied in eight patients with ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s24
更新日期:1989-01-01 00:00:00
abstract::In this article, we report on a nonobese C57BL/6 (B6) mouse model of NIDDM named Akita mouse, characterized by early age onset and autosomal dominant mode of inheritance. At 7 weeks of age, the mean morning blood glucose levels (mmol/l) under ad libitum feeding conditions were significantly higher (P < 0.01, analysis ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.5.887
更新日期:1997-05-01 00:00:00
abstract::Fetuin-A interferes with insulin action in animal studies, but data on fetuin-A and diabetes risk in humans are sparse and the role of nonalcoholic fatty liver disease in this association is unknown. From 2000 to 2006, we prospectively identified 470 matched incident diabetes case-control pairs in the Nurses' Health S...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0372
更新日期:2013-01-01 00:00:00
abstract::Although obesity rates are rapidly rising, caloric restriction remains one of the few safe therapies. Here we tested the hypothesis that obesity-associated disorders are caused by increased adipose tissue as opposed to excess dietary lipids. Fat mass (FM) of lean C57B6 mice fed a high-fat diet (HFD; FMC mice) was "cla...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1621
更新日期:2012-11-01 00:00:00
abstract::Hyperglycemia-induced oxidative stress is detrimental for endothelial cells, contributing to the vascular complications of diabetes. The mitochondrial permeability transition pore (PTP) is an oxidative stress-sensitive channel involved in cell death; therefore, we have examined its potential role in endothelial cells ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.7.2179
更新日期:2005-07-01 00:00:00
abstract::Inadequate beta-cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta-cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS)...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.50.2007.s154
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:Preferential upper-body fat gain, a typical male pattern, is associated with a greater cardiometabolic risk. Regional differences in lipolysis and meal fat storage cannot explain sex differences in body fat distribution. We examined the potential role of the novel free fatty acid (FFA) storage pathway in dete...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0154
更新日期:2011-08-01 00:00:00
abstract::Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial f...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db14-0667
更新日期:2015-04-01 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are incretins secreted by respective K and L enteroendocrine cells after eating and amplify glucose-stimulated insulin secretion (GSIS). This amplification has been termed the "incretin response." To determine the role(s) of K cells for the incretin response...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1188
更新日期:2015-04-01 00:00:00
abstract::Recent evidence supports the strong overlap between genes implicated in monogenic diabetes and susceptibility to type 2 diabetes. Transient neonatal diabetes mellitus (TNDM) is a rare disorder associated with overexpression of genes at a paternally expressed imprinted locus on chromosome 6q24. There are two overlappin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0216
更新日期:2006-08-01 00:00:00
abstract::Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic β-cells in rodents and humans. The full-length isoform (ChREBPα) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0239
更新日期:2015-12-01 00:00:00
abstract::In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with sh...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0908
更新日期:2021-01-07 00:00:00
abstract::Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.7.640
更新日期:1979-07-01 00:00:00
abstract::Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.5.1588
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (P...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0566
更新日期:2011-03-01 00:00:00
abstract::Sterol regulatory element-binding protein (SREBP)-1 transcription factors play a central role in energy homeostasis by promoting glycolysis, lipogenesis, and adipogenesis. The sterol regulatory element-binding protein gene (SREBF)-1 is a good candidate gene for obesity and obesity-related metabolic traits such as type...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.8.2153
更新日期:2004-08-01 00:00:00
abstract::A strong genetic component of the beta-cell defect of type 2 diabetes is undisputed. We recently developed a modification of the classic hyperglycemic clamp to assess beta-cell function in response to various stimuli (10 mmol/l glucose, additional glucagon-like peptide [GLP]-1, and arginine). Subjects at risk for deve...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.2007.s122
更新日期:2002-02-01 00:00:00
abstract::Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0340
更新日期:2014-01-01 00:00:00
abstract::Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.228
更新日期:1999-01-01 00:00:00
abstract::Immune modulation of pancreatic inflammation induces recovery from type 1 diabetes (T1D), but remission was not durable, perhaps because of an inability to sustain the formation and function of new pancreatic β-cells. We have previously shown that Ig-GAD2, carrying GAD 206-220 peptide, induced in hyperglycemic mice im...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1281
更新日期:2013-08-01 00:00:00
abstract::We have studied the factors that influence the efficiency of infection of human fetal and adult pancreatic endocrine cells with adenovirus, murine retrovirus, and lentivirus vectors all expressing the green fluorescent protein (Ad-GFP, MLV-GFP, and Lenti-GFP, respectively). Adenoviral but not retroviral vectors effici...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.4.745
更新日期:1999-04-01 00:00:00
abstract:OBJECTIVE:On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS:Activin A measurement and oral glucose tolerance tes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1493
更新日期:2011-05-01 00:00:00
abstract::Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0375
更新日期:2014-12-01 00:00:00
abstract::The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.12.3524
更新日期:2002-12-01 00:00:00
abstract::Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent o...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.38.12.1512
更新日期:1989-12-01 00:00:00
abstract::Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising ini...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1212
更新日期:2015-04-01 00:00:00
abstract::Children with permanent diabetes are usually assumed to have type 1 diabetes. It has recently been shown that there are genetic subgroups of diabetes that are often diagnosed during the neonatal period but may present later. A recent Italian study proposed that type 1 diabetes is rare before 6 months of age. We aimed ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0094
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide-1 (GLP-1) is a growth and differentiation factor for mature beta-cells and their precursors. However, the overall effect of GLP-1 on increasing beta-cell mass in both in vivo and in vitro conditions is relatively small, and augmenting this effect would be beneficial for the treatment or ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1414
更新日期:2008-03-01 00:00:00