Abstract:
:The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure (n = 51) and atypical diabetic glomerulopathy (n = 75), patients with classic diabetic glomerulopathy (n = 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 +/- 59.8 vs. 166.0 +/- 65.7 vs. 243.8 +/- 82.6 micromol/l; P < 0.001), glomerular matrix fractions (20.8 +/- 6.7 vs. 33.5 +/- 16.8 vs. 39.2 +/- 14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4; P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele (n = 92) and z-2 heterozygotes (n = 77), z-2 homozygotes (n = 17) had elevated plasma creatinine (164.1 +/- 73.7 vs. 190.6 +/- 60.9 vs. 241.1 +/- 86.2 micromol/l; P < 0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs. 3.3; P = 0.026). Overexpression of transforming growth factor-beta1, mesangial cell transdifferentiation by expression of alpha-smooth muscle actin, and aberrant deposition of collagen type IV, fibronectin, and laminin were found in classic diabetic glomerulopathy. These data suggest genetic, biochemical, pathophysiological, and clinical correlations among the aldose reductase gene, extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency. Gene mutation, cellular transdifferentiation, growth factor upregulation, extracellular matrix expansion, and glomerular filtration impairment are the primary abnormalities in type 2 diabetic patients with nephropathy.
journal_name
Diabetesjournal_title
Diabetesauthors
Zhao HL,Tong PC,Lai FM,Tomlinson B,Chan JCdoi
10.2337/diabetes.53.11.2984subject
Has Abstractpub_date
2004-11-01 00:00:00pages
2984-91issue
11eissn
0012-1797issn
1939-327Xpii
53/11/2984journal_volume
53pub_type
杂志文章相关文献
DIABETES文献大全abstract::The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP-sensitive K+ channels. It is an ATP-binding cassette protein comprising 17 transmembrane helices. SUR is endowed with binding sites for channel blockers like the antidiabetic sulfonylurea glibenclamide and for the chemically very heterogeneous ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.suppl_3.s128
更新日期:2004-12-01 00:00:00
abstract::A group of insulin-dependent diabetic patients was studied in order to determine the possible short-term regulatory effect of insulin and that of an antilipolytic drug on serum triglycerides. Subcutaneous crystalline insulin (one third of the usual morning dose of intermediate long-acting insulin, NPH) and an oral dos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.7.615
更新日期:1977-07-01 00:00:00
abstract::Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the ro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0134
更新日期:2012-06-01 00:00:00
abstract::Monogenic human disorders have been used as paradigms for complex genetic disease and as tools for establishing important insights into mechanisms of gene regulation and transcriptional control. Maturity-onset diabetes of the young (MODY) is a monogenic dominantly inherited form of diabetes that is characterized by de...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.7.2329
更新日期:2002-07-01 00:00:00
abstract::NADPH facilitates glucose-stimulated insulin secretion (GSIS) in pancreatic islets (PIs) of β-cells through an as yet unknown mechanism. We found NADPH oxidase isoform 4 (NOX4) to be the main producer of cytosolic H2O2, which is essential for GSIS; an increase in ATP alone was insufficient for GSIS. The fast GSIS phas...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-1130
更新日期:2020-07-01 00:00:00
abstract::The "M" variant of the encephalomyocarditis (EMC) virus causes a diabetes-like disease in some, but not all, strains of mice. The genetic basis for either resistance or susceptibility to the diabetogenic effect of the virus is not known. After infection with EMC, C57BL/6 mice seldom develop hyperglycemia and the insul...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.5.451
更新日期:1981-05-01 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::Tight glycemic control by intensive insulin therapy effectively delays the onset and slows the progression of diabetic complications but is associated with frequent dose adjustments and a high incidence of hypoglycemia. Successful pancreas transplantation corrects abnormal glucose metabolism but subjects patients to m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.3.342
更新日期:1996-03-01 00:00:00
abstract::Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1281
更新日期:2018-09-01 00:00:00
abstract::Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.161
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. RESEARCH DESIGN AND METHODS:Forearm skeletal musc...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0857
更新日期:2008-07-01 00:00:00
abstract::A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are use...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.3.169
更新日期:1980-03-01 00:00:00
abstract:CONTEXT:Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases. The aim of this study was to determine whether circulating FASN could be a biomarker of overnutrition-induced metabolic stress and insulin resistance in common metabolic disorders. RESEARCH DESIGN AND METHODS:Circu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1756
更新日期:2010-06-01 00:00:00
abstract::The hormonal responses to low-level exercise in pregnancy have been studied in 13 insulin-requiring diabetic patients and 42 control subjects. We found no significant changes in plasma glucose, epinephrine, glucagon, or FFA with this level of exercise in the study group and control subjects; but plasma norepinephrine ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.2.s78
更新日期:1985-06-01 00:00:00
abstract::The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi18-0036
更新日期:2019-03-01 00:00:00
abstract::The interaction between insulin and its receptor was investigated using both monoclonal and polyclonal anti-insulin antibodies. After covalent cross-linking of 125I-insulin to the insulin receptor on cultured human lymphocytes (IM-9 cells) using disuccinimidyl suberate, we inquired whether the insulin-receptor complex...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.8.778
更新日期:1984-08-01 00:00:00
abstract::Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in hum...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0940
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subseq...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1578
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo are less well characterized....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0706
更新日期:2008-02-01 00:00:00
abstract::Prostaglandin E (PGE) infusion in normal man inhibits the acute insulin response to glucose. In order to determine whether endogenously released PGE might also inhibit insulin secretion, glucose-stimulated insulin responses were investigated in normal volunteers after furosemide (40 mg i.v.), a stimulator of endogenou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.9.841
更新日期:1979-09-01 00:00:00
abstract::The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and surviva...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1475
更新日期:2003-06-01 00:00:00
abstract::We report the results of cross-sectional, prospective, and longitudinal studies identifying etiologic metabolic factors in the susceptibility to type 2 diabetes mellitus of the Pima Indians of Arizona, whose prevalence and incidence rates of the disease are the highest in the world. Diabetic Pima Indians are metabolic...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.2007.s262
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVE:Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary hu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0583
更新日期:2008-06-01 00:00:00
abstract::We have applied cell-attached capacitance measurements to investigate whether synaptic-like microvesicles (SLMVs) undergo regulated exocytosis in insulinoma and primary pancreatic beta-cells. SLMV and large dense-core vesicle (LDCV) exocytosis was increased 1.6- and 2.4-fold upon stimulation with 10 mmol/l glucose in ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.3.736
更新日期:2005-03-01 00:00:00
abstract::We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1217
更新日期:1989-10-01 00:00:00
abstract::We used hepatic balance and tracer ([3H]glucose) techniques to examine the impact of "breakfast" on hepatic glucose metabolism later in the same day. From 0-240 min, 2 groups of conscious dogs (n = 9 dogs/group) received a duodenal infusion of glucose (GLC) or saline (SAL), then were fasted from 240-360 min. Three dog...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1308
更新日期:2017-05-01 00:00:00
abstract::On the basis of the positive outcome of animal experiments, several large placebo-controlled trials are underway and aiming for the first time at the prevention of an immune-mediated disease, type 1 diabetes. The first of these trials, The Deutsche Nicotinamide Intervention Study (DENIS), evaluated the clinical effica...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.2337/diabetes.47.6.980
更新日期:1998-06-01 00:00:00
abstract::Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.9.1099
更新日期:1990-09-01 00:00:00
abstract::Leptin, a recently identified hormone, is believed to reduce appetite and maintain body weight. The mRNA of leptin is expressed only in mature adipose cells. To clarify the regulation of leptin gene expression in adipocytes, 3T3-L1 adipocytes were treated for 16 h with various agents known to modulate lipid metabolism...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.12.1744
更新日期:1996-12-01 00:00:00
abstract::To study the relationship between the aldose reductase gene and diabetic complications, an (A-C)n dinucleotide repeat sequence 2.1 kb upstream of the transcription start site of this gene was identified and studied. There are seven alleles at this locus with a polymorphism information content of 0.73 and a heterozygos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.44.7.727
更新日期:1995-07-01 00:00:00