Abstract:
:Syngeneic pancreatic islet grafts in diabetic NOD mice are infiltrated by mononuclear leukocytes, beta-cells are selectively destroyed, and autoimmune diabetes recurs. This model was used to identify islet graft-infiltrating mononuclear leukocytes associated with beta-cell destruction and diabetes recurrence. We compared cell surface antigen and cytokine-producing phenotypes of mononuclear leukocytes in islet grafts from NOD mice that were protected from diabetes recurrence by complete Freund's adjuvant (CFA) administration (beta-cell nondestructive insulitis) and in islet grafts from control phosphate-buffered saline (PBS)-injected NOD mice (beta-cell destructive insulitis). Islet grafts from CFA-injected mice contained fewer CD4+ and CD8+ cells and more B cells; also fewer interferon gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha)-positive cells and more IL-4 and IL-10 positive cells. By performing two-color immunostaining of cell surface antigens and intracellular IFN-gamma, we found that IFN-gamma positive cells in islet grafts from CFA- and PBS-injected mice were approximately equally divided between CD4+ and CD8+ T-cell subsets. Also, the frequencies of both CD4+ IFN-gamma + and CD8+ IFN-gamma + cells were decreased in islet grafts from CFA-injected mice. These findings suggest that destruction of beta-cells in syngeneic islets transplanted into NOD mice is promoted by cells producing Th1-type cytokines (IFN-gamma, IL-2, and TNF-alpha) and prevented by cells producing TH2-type cytokines (IL-4 and IL-10). Furthermore, both CD4+ and CD8+ IFN-gamma-producing T-cells in the islet grafts appear to be involved in beta-cell destruction and diabetes recurrence.
journal_name
Diabetesjournal_title
Diabetesauthors
Suarez-Pinzon W,Rajotte RV,Mosmann TR,Rabinovitch Adoi
10.2337/diab.45.10.1350subject
Has Abstractpub_date
1996-10-01 00:00:00pages
1350-7issue
10eissn
0012-1797issn
1939-327Xjournal_volume
45pub_type
杂志文章相关文献
DIABETES文献大全abstract::Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation of BK-β(1) expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1658
更新日期:2012-07-01 00:00:00
abstract::Metabolic interactions between glucose and amino acids were studied with isolated rat islets using glucose utilization and lactate formation as indicators. Certain amino acids (8-10 mM) are capable of greatly stimulating lactate formation from 5mM glucose. On a molar basis L-isoleucine is the most potent stimulator in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.5.476
更新日期:1975-05-01 00:00:00
abstract::The uptake of 2-deoxy-D-[1-14C]-glucose, in the presence and absence of insulin, was measured in adipocytes from normal and streptozotocin-diabetic animals, over a wide temperature range (25-45 degrees C). Optimum temperatures for uptake in the presence of maximally stimulating insulin concentrations occurred near phy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.3.258
更新日期:1984-03-01 00:00:00
abstract::Variation in the calpain 10 gene has recently been shown to be associated with type 2 diabetes by positional cloning. Since then, studies on calpain 10 have been started in correlation with diabetes and insulin-mediated signaling. In this review, the activation mechanism of calpain by calcium ions, which is essential ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.2007.s12
更新日期:2004-02-01 00:00:00
abstract::Based on studies of both man and rat, it is proposed that at least three distinct syndromes of hypertriglyceridemia occur as the result of abnormalities of carbohydrate metabolism. We believe that these syndromes are the predictable results of the changes in plasma insulin and/or free fatty acid (FFA) concentration th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.2.s66
更新日期:1981-01-01 00:00:00
abstract::Increased fat mass, abdominal adiposity, and insulin resistance are typical findings in aging mammals and are frequently associated with leptin resistance and increased plasma leptin levels. To examine whether leptin's failure in aging is due to aging per se or to changes in body fat mass or distribution, we studied a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.1016
更新日期:2002-04-01 00:00:00
abstract::Previous studies have demonstrated that the ventromedial hypothalamus (VMH) plays a critical role in sensing and responding to systemic hypoglycemia. To evaluate the mechanisms of defective counterregulation caused by iatrogenic hypoglycemia and diabetes per se, we delivered 2-deoxy-glucose (2-DG) via microdialysis in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.3.584
更新日期:1999-03-01 00:00:00
abstract::Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.704
更新日期:2002-03-01 00:00:00
abstract::In type 2 diabetes, impaired insulin-induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response. Previously, we reported that this response was negatively regulated by G protein-coupled receptor kinase 2 (GRK2). In this study, we investigated whether/how in aortas from...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1729
更新日期:2012-08-01 00:00:00
abstract::Genes of the Notch signaling pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. The Notch ligand Delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of multipotent progenitors in the developing pancreas, and loss of D...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0795
更新日期:2020-05-01 00:00:00
abstract::Exercise-induced hyperinsulinism (EIHI) is an autosomal dominant disorder characterized by inappropriate insulin secretion in response to vigorous physical exercise or pyruvate injection. Activating mutations in the monocarboxylate transporter-1 (MCT1, SLC16A1) promoter have been linked to EIHI. Expression of this pyr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1531
更新日期:2012-07-01 00:00:00
abstract::We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1588
更新日期:2017-07-01 00:00:00
abstract::Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.10.1156
更新日期:1995-10-01 00:00:00
abstract::Rosiglitazone therapy improves insulin sensitivity and glucose uptake in patients with uncomplicated type 2 diabetes. In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. The aim was to test whether ...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.54.9.2787
更新日期:2005-09-01 00:00:00
abstract::Type 2 diabetes and skeletal muscle insulin resistance have been linked to accumulation of the intramyocellular lipid-intermediate diacylglycerol (DAG). However, recent animal and human studies have questioned such an association. Given that DAG appears in different stereoisomers and has different reactivity in vitro,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0655
更新日期:2016-10-01 00:00:00
abstract::Type 2 diabetes is characterized by islet amyloid deposits, which are primarily composed of the amyloidogenic human form of islet amyloid polypeptide (IAPP, amylin). The mechanism of islet amyloido-genesis is not known, but other products (e.g., apolipoprotein E and perlecan) contained within islet amyloid may be nece...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.10.1962
更新日期:1999-10-01 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::Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the p...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db05-1685
更新日期:2006-05-01 00:00:00
abstract::Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db11-1213
更新日期:2012-01-01 00:00:00
abstract::We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0742
更新日期:2015-08-01 00:00:00
abstract::The use of HIV protease inhibitors (PIs) has been associated with several metabolic changes, including lipodystrophy, hyperlipidemia, and insulin resistance. The etiology of these adverse effects remains unknown. PIs have recently been found to cause acute and reversible inhibition of GLUT4 activity in vitro. To deter...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.937
更新日期:2002-04-01 00:00:00
abstract::Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22-producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0592
更新日期:2020-08-01 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::Insulin-secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific subpopulations with d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi17-0040
更新日期:2018-04-01 00:00:00
abstract::Improvement of glycemic status by insulin is associated with profound changes in amino acid metabolism in type 1 diabetes. In contrast, a dissociation of insulin effect on glucose and amino acid metabolism has been reported in type 2 diabetes. Type 2 diabetic patients are reported to have reduced muscle oxidative enzy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.8.2395
更新日期:2002-08-01 00:00:00
abstract::GLP-1 and incretin mimetics, such as exenatide, have been shown to attenuate hepatocyte steatosis in vivo and in vitro, but the specific underlying mechanism is unclear. SIRT1, an NAD(+)-dependent protein deacetylase, has been considered as a crucial regulator in hepatic lipid homeostasis by accumulated studies. Here,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0263
更新日期:2014-11-01 00:00:00
abstract::Fetal hyperinsulinemia causes fetal arterial hypoxia because fetal O2 use increases, whereas the supply of O2 to the fetus does not. To find which of the fetal tissues accounts for such an increase in fetal O2 use, we examined the effect of plasma hyperinsulinemia on O2, glucose, and lactate use by the hindquarters of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.5.597
更新日期:1989-05-01 00:00:00
abstract:OBJECTIVE:To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1112
更新日期:2009-02-01 00:00:00
abstract::IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets. In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2be...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.suppl_2.s46
更新日期:2005-12-01 00:00:00
abstract::The effect of elevated glucagon concentrations on insulin requirements and on blood glucose concentrations was studied in five insulin-requiring diabetic subjects during feedback control of hyperglycemia with an automated glucose-controlled insulin infusion system (artificial endocrine pancreas) for six to eight hours...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.6.649
更新日期:1978-06-01 00:00:00