Abstract:
:Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic properties and, therefore, have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow-derived MSCs have on neonatal porcine islets (NPIs) in vitro and determined islet engraftment and metabolic outcomes when cotransplanted in a mouse model. NPIs cocultured with MSCs had greater cellular insulin content and increased glucose-stimulated insulin secretion. NPIs were cotransplanted with or without MSCs in diabetic B6.129S7-Rag1tm1Mom/J mice. Blood glucose and weight were monitored until reversal of diabetes; mice were then given an oral glucose tolerance test. Islet grafts were assessed for the degree of vascularization and total cellular insulin content. Cotransplantation of NPIs and MSCs resulted in significantly earlier normoglycemia and vascularization, improved glucose tolerance, and increased insulin content. One experiment conducted with MSCs from a donor with an autoimmune disorder had no positive effects on transplant outcomes. Cotransplantation of human MSCs with NPIs demonstrated a beneficial metabolic effect likely as a result of earlier islet vascularization and improved islet engraftment. In addition, donor pathology of MSCs can influence the functional capacity of MSCs.
journal_name
Diabetesjournal_title
Diabetesauthors
Hayward JA,Ellis CE,Seeberger K,Lee T,Salama B,Mulet-Sierra A,Kuppan P,Adesida A,Korbutt GSdoi
10.2337/db16-1068subject
Has Abstractpub_date
2017-05-01 00:00:00pages
1312-1321issue
5eissn
0012-1797issn
1939-327Xpii
db16-1068journal_volume
66pub_type
杂志文章相关文献
DIABETES文献大全abstract::The clearing of monoclonal and polyclonal and anti-insulin antibodies from homogeneous solutions at 100,000 X g was used to estimate the size of soluble insulin-antibody complexes at physiologic concentrations. Monoclonal antibodies cleared as a uniform population of 6.6 S independent of the insulin concentration. Pol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.8.799
更新日期:1985-08-01 00:00:00
abstract::Circulating insulin autoantibodies (INSAAb) were measured in discordant monozygotic twins, first-degree relatives, and other groups at "high risk" for the development of insulin-dependent diabetes mellitus (IDDM), and these results correlated with both islet cell antibody (ICAb) status and beta cell function. INSAAb w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.2.139
更新日期:1986-02-01 00:00:00
abstract::To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.10.1305
更新日期:1990-10-01 00:00:00
abstract::Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.11.2240
更新日期:1999-11-01 00:00:00
abstract::We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0-5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucose-induced insulin secre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.10.1170
更新日期:1990-10-01 00:00:00
abstract::Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permselectivity of glomerular basement membrane (GBM) plays an important role in DN pathogenesis. Heparanase is the predominant enzyme that degrades heparan sulfate (HS), the main polysaccharide of the GBM. Loss of GBM HS in dia...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1024
更新日期:2012-01-01 00:00:00
abstract::Cardiac failure is a major cause of death in patients with type 2 diabetes, but the molecular mechanism that links diabetes to heart failure remains unclear. Insulin resistance is a hallmark of type 2 diabetes, and insulin receptor substrates 1 and 2 (IRS1 and IRS2) are the major insulin-signaling components regulatin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0095
更新日期:2013-11-01 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::We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.38.6.704
更新日期:1989-06-01 00:00:00
abstract::This article presents a model for the HLA effect in insulin-dependent diabetes mellitus (IDDM) that is almost the mirror image of a model suggested by Nepom. In the Nepom model, the products of certain HLA alleles are associated with IDDM because they bind and present a specific peptide or peptides so as to induce an ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.41.2.123
更新日期:1992-02-01 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::To ascertain whether the dawn phenomenon occurs in nondiabetic individuals and, if so, whether it is due to an increase in glucose production or a decrease in glucose utilization, we determined plasma concentrations of glucose, insulin, C-peptide, and counterregulatory hormones, as well as rates of glucose production,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.12.1150
更新日期:1984-12-01 00:00:00
abstract::Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). W...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db10-0902
更新日期:2012-02-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha) and hyperglycemia both impair insulin sensitivity in vivo. This may be secondary to stimulation of adipose tissue lipolysis and consequent increased circulating free fatty acids (FFAs). Here we report that neither TNF-alpha nor glucose alone has a pronounced effect on lipolysis ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.1.74
更新日期:2004-01-01 00:00:00
abstract::Brain lactate may be involved in the development of impaired awareness of hypoglycemia (IAH), a condition that affects approximately 25% of patients with type 1 diabetes and increases the risk of severe hypoglycemia. The aim of this study was to investigate the effect of acute hypoglycemia on brain lactate concentrati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0068
更新日期:2016-06-01 00:00:00
abstract::GLUT2 glucose transporter mRNA has been shown to be underexpressed in pancreatic islets of numerous animal models of non-insulin-dependent diabetes mellitus (NIDDM). It has been proposed that this molecular defect contributes to the pathogenesis of diabetes, although information concerning the expression of GLUT2 in h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.12.1369
更新日期:1995-12-01 00:00:00
abstract::The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.12.1040
更新日期:1980-12-01 00:00:00
abstract::The responsiveness of the isolated perfused rat liver to different metabolic effects of insulin was investigated during recycling perfusion. Infusion of porcine insulin at rates of 6, 9, 16 and 33 mU/hr. resulted in stable perfusate insulin levels averaging 41, 72, 120 and 229 muU/ml., respectively. Since the portal v...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.2.225
更新日期:1975-02-01 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::In this study, 92% of patients' serums known to contain antibodies against islet cells, including the Juvenile Diabetes Foundation provisional reference serum, had antibodies reacting with gastrointestinal carcinoid tumors. Twelve percent of the control serums from healthy individuals bound to carcinoid cells, and 2% ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.5.667
更新日期:1989-05-01 00:00:00
abstract::Rapamycin is used frequently in both transplantation and oncology. Although historically thought to have little diabetogenic effect, there is growing evidence of β-cell toxicity. This Review draws evidence for rapamycin toxicity from clinical studies of islet and renal transplantation, and of rapamycin as an anticance...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db13-0106
更新日期:2013-08-01 00:00:00
abstract::Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intrahepatic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.3.201
更新日期:1977-03-01 00:00:00
abstract::Protein kinase C (PKC) has been suggested as a mediator of insulin's effect on glucose transport, and PKC-mediated modulation of tyrosine kinase activity in the insulin receptor has been implicated in regulating the insulin sensitivity of tissues. Because skeletal muscle is a major target of insulin action, we examine...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.5.499
更新日期:1988-05-01 00:00:00
abstract::Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0828
更新日期:2020-02-01 00:00:00
abstract::The association of type 1 diabetes with the insulin gene (IDDM2 locus) has been mapped to a short haplotype encompassing two single nucleotide polymorphisms (SNPs) in perfect linkage disequilibrium (r(2) = 1) with each other and with the two allele classes at the variable number of tandem repeats (VNTR) polymorphism u...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0402
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS:Characterization of clinical and biochemical parameters and β-cell function of 411 Medalists with correlation wi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0676
更新日期:2010-11-01 00:00:00
abstract::The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. As a step toward understanding the molecular basis of glucokinase (GK) gene regulation, we assessed the structure and regulation of the human GK gene beta-cell-type promote...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.11.1478
更新日期:1996-11-01 00:00:00
abstract::Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.1.s10
更新日期:1980-01-01 00:00:00
abstract::We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.8.981
更新日期:1989-08-01 00:00:00
abstract::Recent studies have identified that the activation of protein kinase C (PKC) and increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated with many vascular abnormalities in retinal, renal, and cardiovascular tissues. Among the various PKC isoforms, the beta- and delta-isoforms appear to be acti...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.6.859
更新日期:1998-06-01 00:00:00