Abstract:
:Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36.
journal_name
Diabetesjournal_title
Diabetesauthors
Collison M,Glazier AM,Graham D,Morton JJ,Dominiczak MH,Aitman TJ,Connell JM,Gould GW,Dominiczak AFdoi
10.2337/diabetes.49.12.2222subject
Has Abstractpub_date
2000-12-01 00:00:00pages
2222-6issue
12eissn
0012-1797issn
1939-327Xjournal_volume
49pub_type
杂志文章相关文献
DIABETES文献大全abstract::Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/wee...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.12.2154
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVE:The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS:We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Ak...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1795
更新日期:2011-09-01 00:00:00
abstract::Nerve conduction and electromyography (EMG) of insulin-dependent (type 1) diabetic patients with end-stage nephropathy was studied before and up to 10 yr after kidney transplantation (KTx). A series of nondiabetic KTx patients served as a comparison group. Motor nerve conduction velocity (NCV) was measured in the ulna...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.9.1247
更新日期:1988-09-01 00:00:00
abstract::Sera from rats inoculated with in vitro glucosylated rat skin acid-soluble collagen were evaluated for specific antibody response using the enzyme-linked immunosorbent assay. The data indicate that the altered protein is capable of eliciting the production of antibodies, but unmodified collagen is not. The specificity...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.12.1182
更新日期:1983-12-01 00:00:00
abstract::Antibodies to single stranded (SS-) and double stranded (DS-) DNA and RNA were determined by a passive microhemagglutination assay in sera from 80 children with juvenile-onset diabetes mellitus (JDM) and 129 children with asthma. The latter group was chosen for comparison with the JDM group because of their increased ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.11.1105
更新日期:1978-11-01 00:00:00
abstract:OBJECTIVE:Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low-circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investiga...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1338
更新日期:2010-04-01 00:00:00
abstract::A cohort of 372 insulin-dependent diabetic children, diagnosed between October 1949 and December 1960, were followed-up until December 1976 by the same team of physicians. At the time of diagnosis all patients were under 16 yr of age and were given standardized treatment which did not change from 1949 to 1976. The the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.3.175
更新日期:1981-03-01 00:00:00
abstract::We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IR...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.8.1949
更新日期:2001-08-01 00:00:00
abstract::Islet transplantation is a potential treatment for type 1 diabetes, but the shortage of donor organs limits its routine application. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-4Ig, under the control of the porcine insul...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1325
更新日期:2012-06-01 00:00:00
abstract::Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows: Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rap...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.1.1
更新日期:1975-01-01 00:00:00
abstract::Continuous subcutaneous insulin infusion (CSII) was combined with antirejection therapy in four diabetic recipients of pancreas and kidney grafts with persisting hyperglycemia due to pancreas rejection. In three of the patients, full function of the pancreas was restored after as many as 40, 86, and 139 days of CSII. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s71
更新日期:1989-01-01 00:00:00
abstract::Treatment of isolated, perifused rat islets with exogenous PLA2 in amounts ranging from 1 to 1000 mU/ml caused a dose-dependent increase in the rate of insulin secretion. This effect of PLA2 was rapid and seen in the absence of added exogenous fuel. It differed from glucose-induced insulin release in temporal pattern:...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.5.471
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extra...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0822
更新日期:2009-03-01 00:00:00
abstract::There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.1.113
更新日期:1997-01-01 00:00:00
abstract::The gene for insulin-degrading enzyme (IDE) represents a strong positional and biological candidate for type 2 diabetes susceptibility. IDE maps to chromosome 10q23.3, a region linked to diabetes in several populations; the rat homolog has been directly implicated in diabetes susceptibility; and known functions of IDE...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.5.1300
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVE:The G-protein-coupled receptor Gpr40 is expressed in beta-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion. However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1/PDX1 was recently shown to bi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0307
更新日期:2008-09-01 00:00:00
abstract::Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endoto...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1491
更新日期:2007-07-01 00:00:00
abstract::I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks ol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.10.969
更新日期:1978-10-01 00:00:00
abstract::Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancrease. Addition of toxin, 10 mug./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppress...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.8.645
更新日期:1976-08-01 00:00:00
abstract::Coronavirus disease 2019 (COVID-19) is a novel threat that seems to result from the collusion between a new pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and an existing pandemic of metabolic disease driven by obesity. This Perspective explores the evolving epidemiological, clinical, biologi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi19-0023
更新日期:2020-09-01 00:00:00
abstract::This cross-sectional study evaluated the relationship between 1) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1453
更新日期:2017-09-01 00:00:00
abstract::We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. MC3-R and MC4-R were measured by quantitative autoradiography in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.2.267
更新日期:1999-02-01 00:00:00
abstract::The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The study was performed in 60 women with normal oral glucose tolerance. Differences in insulin-me...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.2.244
更新日期:1998-02-01 00:00:00
abstract::Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is probably determined by renal hemodynamic abnormalities and by a genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angioten...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.3.384
更新日期:1994-03-01 00:00:00
abstract::Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotoci...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1042
更新日期:2018-03-01 00:00:00
abstract::Enterovirus infections, implicated in the pathogenesis of type 1 diabetes in a number of studies, may precipitate the symptoms of clinical diabetes and play a role in the initiation of the beta-cell damaging process. The aim of this study was to evaluate whether cellular immune responses to enterovirus antigens are ab...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.8.1308
更新日期:2000-08-01 00:00:00
abstract::Specific allelic associations vary among ethnic groups. We studied the distribution of HLA-A,-B,-C, and -DR antigens in 34 Japanese juvenile-onset diabetic patients. The focus of our current work was HLS-DR antigens because there have been few studies of Japanese with this disease. A significant increase in the freque...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.2.105
更新日期:1982-02-01 00:00:00
abstract::Little is known about the molecular mechanisms underlying age-dependent deterioration in β-cell function. We now demonstrate that age-dependent impairment in insulin release, and thereby glucose homeostasis, is associated with subtle changes in Ca(2+) dynamics in mouse β-cells. We show that these changes are likely to...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1855
更新日期:2014-12-01 00:00:00
abstract::The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein respon...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.46.12.2082
更新日期:1997-12-01 00:00:00
abstract::Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1320
更新日期:1989-10-01 00:00:00