Abstract:
:Islet transplantation for the treatment of autoimmune diabetes is more difficult because of the additional barrier presented by the autoimmunity. We tested the ability of hamster anti-rat CD154 to prevent recurrence of diabetes in renal subcapsular islet isografts in DR-BB (RT1uu) rats with established autoimmune diabetes. Experimental animals with established diabetes received intravenous injections of 15 mg/kg anti-CD154 on a specified schedule starting 2 days before renal subcapsular transplantation of an islet isograft. Control animals received either saline or hamster IgG. Plasma glucose levels >250 mg/dl over 3 days were used to indicate the recurrence of diabetes. Rats that received saline (n = 5) or control antibody (n = 3) had a recurrence of diabetes 6-11 days after transplantation. Histological examination of islet isografts from these rats showed complete destruction of the insulin-producing portion of the isograft with residual cells positive for glucagon. Recipient rats that received anti-CD154 at the 15-mg/kg dosage (n = 6) did not have a recurrence of diabetes for 308-461 days after transplantation. Islet isografts removed from the rats showed low levels of insulin immunoreactivity, high levels of insulin mRNA, and focal infiltration with lymphocytes but no evidence of islet destruction. Mean peak antibody concentration was 266 microg/ml and returned to undetectable levels by 67-88 days after transplantation. Rats that received anti-CD154 starting at 4-7 days after transplantation had a recurrence of diabetes within 11 days of the isotransplantation. Therefore, anti-CD154 as the sole immunomodulator prevented the recurrence of diabetes in islet isografts in rats with established autoimmune diabetes. This suggests that CD40/CD154 blockade is effective in preventing the insulitis or the effector phase of autoimmune diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Kover KL,Geng Z,Hess DM,Benjamin CD,Moore WVdoi
10.2337/diabetes.49.10.1666subject
Has Abstractpub_date
2000-10-01 00:00:00pages
1666-70issue
10eissn
0012-1797issn
1939-327Xjournal_volume
49pub_type
杂志文章相关文献
DIABETES文献大全abstract::Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0777
更新日期:2013-07-01 00:00:00
abstract::C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin be...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0733
更新日期:2006-02-01 00:00:00
abstract::The sustained expression of the MAFB transcription factor in human islet β-cells represents a distinct difference in mice. Moreover, mRNA expression of closely related and islet β-cell-enriched MAFA does not peak in humans until after 9 years of age. We show that the MAFA protein also is weakly produced within the juv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0903
更新日期:2019-02-01 00:00:00
abstract::Highly angiogenic bone marrow mononuclear cell-derived spheroids (BM-spheroids), formed by selective proliferation of the CD31+CD14+CD34+ monocyte subset via three-dimensional (3D) culture, have had robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the effica...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0705
更新日期:2018-03-01 00:00:00
abstract::Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to dete...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1384
更新日期:2017-06-01 00:00:00
abstract::Pioglitazone is widely used for the treatment of diabetic patients with insulin resistance. The mechanism of pioglitazone to improve insulin sensitivity is not fully understood. Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistanc...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1039
更新日期:2007-03-01 00:00:00
abstract::Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE recept...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.5.1214
更新日期:2001-05-01 00:00:00
abstract::Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.6.736
更新日期:1992-06-01 00:00:00
abstract::Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.11.1345
更新日期:1994-11-01 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::With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studie...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.7.1209
更新日期:2000-07-01 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 development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.34
更新日期:1999-01-01 00:00:00
abstract::In vivo studies were undertaken in rats to provide evidence of the neural nature, tentative localization and mode of excitation of the insulin-sensitive central nervous system (CSN) glucoregulator center. In rats under light barbiturate anesthesia minute amounts of insulin injected into the carotid artery resulted in ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.4.328
更新日期:1975-04-01 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::Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of vari...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.44.3.330
更新日期:1995-03-01 00:00:00
abstract::Plasma glucagon response to glucose in diabetic subjects was observed before and after treatment. In normal subjects, plasma glucagon concentrations decreased substantially after an oral glucose load. In all diabetic patients before treatment, plasma glucagon was not suppressed and rather tended to rise paradoxically ...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.27.12.1145
更新日期:1978-12-01 00:00:00
abstract::Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, primitive defect in proinsulin processing or be secondary to increased demand on β-cells (hyperinsulinemia secondary to insulin resistance). An alternative way to investigate the relation between rel...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0279
更新日期:2018-11-01 00:00:00
abstract::The effect of nonenzymatic glycosylation on the biologic function of human antithrombin III was evaluated using a chromogenic thrombin substrate assay in the presence of catalytic amounts of heparin. Experimental conditions that increased the rate of nonenzymatic protein glycosylation were associated with decreases in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.6.532
更新日期:1984-06-01 00:00:00
abstract::To clarify the event that is involved in the pathogenesis of impaired glucose tolerance (IGT), we studied 15 individuals with IGT and 15 subjects with normal tolerance using the minimal model approach. Our IGT subjects were characterized by normal insulin secretory responses to oral glucose and mild impairments in ins...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.43.10.1211
更新日期:1994-10-01 00:00:00
abstract::We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 hea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.8.2474
更新日期:2002-08-01 00:00:00
abstract::Although most patients with type 1 diabetes (T1D) continue to produce small amounts of insulin decades after disease onset, very few β-cells persist within their pancreata. Consequently, the source of persistent insulin secretion within T1D remains unclear. We hypothesized that low-level insulin content within non-β-c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0305
更新日期:2019-03-01 00:00:00
abstract::Activation of the receptor for advanced glycation end products (RAGE) reportedly triggers a variety of proinflammatory responses. However, our previous work revealed that RAGE-binding AGEs free of endotoxin were incapable of inducing vascular cell adhesion molecule-1 (VCAM-1) or tumor necrosis factor-alpha (TNF-alpha)...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.743
更新日期:2004-03-01 00:00:00
abstract::Growth hormone (GH) and IGFs have a long distinguished history in diabetes, with possible participation in the development of renal complications. The implicated effect of GH in diabetic end-stage organ damage may be mediated by growth hormone receptor (GHR) or postreceptor events in GH signal transduction. The presen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.7.2270
更新日期:2002-07-01 00:00:00
abstract::The significance of the portohepatic glucosensors for counterregulation in deep hypoglycemia (i.e., glycemia < 2.8 mM) was studied in chronically cannulated male mongrel dogs in the conscious state. A total of 16 experiments were carried out on 6 dogs using the liver clamp technique under hyperinsulinemic conditions (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.8.1052
更新日期:1994-08-01 00:00:00
abstract::Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on β-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell-specific deficiency of TL...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0373
更新日期:2021-02-01 00:00:00
abstract::Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1025
更新日期:2017-03-01 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::Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 20...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1557
更新日期:2003-06-01 00:00:00
abstract::Type 1 diabetes is a major histocompatibility complex (MHC) class II-associated autoimmune disease mediated by beta-cell-specific T-cells and characterized by circulating autoantibodies to beta-cell molecules. In the BB/Wor diabetes-prone (DP) rat, type 1 diabetes develops spontaneously with an incidence of >90%. BB d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.975
更新日期:1999-05-01 00:00:00