Abstract:
:We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD34(+) cells from patients with diabetes were compared with those of nondiabetic controls. Ang-(1-7) restored impaired migration and nitric oxide bioavailability/cGMP in response to stromal cell-derived factor and resulted in a decrease in NADPH oxidase activity. The survival and proliferation of CD34(+) cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. ACE2 expression was lower, and ACE2 activators xanthenone and diminazine aceturate were less effective in inducing the migration in cells from patients with diabetes compared with controls. Ang-(1-7) overexpression by lentiviral gene modification restored both the in vitro vasoreparative functions of diabetic cells and the in vivo homing efficiency to areas of ischemia. A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. Thus, ACE2/Ang-(1-7)\Mas pathway activation corrects existing diabetes-induced CD34(+) cell dysfunction and also confers protection from development of this dysfunction.
journal_name
Diabetesjournal_title
Diabetesauthors
Jarajapu YP,Bhatwadekar AD,Caballero S,Hazra S,Shenoy V,Medina R,Kent D,Stitt AW,Thut C,Finney EM,Raizada MK,Grant MBdoi
10.2337/db12-0808subject
Has Abstractpub_date
2013-04-01 00:00:00pages
1258-69issue
4eissn
0012-1797issn
1939-327Xpii
db12-0808journal_volume
62pub_type
杂志文章相关文献
DIABETES文献大全abstract::We have shown previously that palmitate treatment of C2C12 skeletal muscle myotubes causes inhibition of the protein kinase B (PKB) pathway and hence reduces insulin-stimulated glycogen synthesis through the elevation of intracellular ceramide levels. Ceramide is known to activate both atypical protein kinase C (aPKC)...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.10.2210
更新日期:2001-10-01 00:00:00
abstract::Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.12.1618
更新日期:1988-12-01 00:00:00
abstract:OBJECTIVE:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0705
更新日期:2011-03-01 00:00:00
abstract::Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.8.2424
更新日期:2005-08-01 00:00:00
abstract::Hypoglycemia causes substantial morbidity and some mortality in insulin-dependent diabetes mellitus (IDDM). It is often the limiting factor in attempts to achieve euglycemia. The prevention or correction of hypoglycemia normally involves both dissipation of insulin and activation of glucose counterregulatory systems. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.9.1193
更新日期:1989-09-01 00:00:00
abstract::This study examines whether the loss of metabolic control in initially normalized islet transplants can result from the inadequate composition of the donor tissue. Streptozotocin-induced diabetic rats were followed for 64 weeks after the intraportal injection of islet isografts with different composition. The implanta...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.12.1814
更新日期:1996-12-01 00:00:00
abstract::We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concent...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.5.639
更新日期:1990-05-01 00:00:00
abstract::The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db15-0318
更新日期:2015-07-01 00:00:00
abstract::Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in patients with newly...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1227
更新日期:2018-10-01 00:00:00
abstract::This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0261
更新日期:2017-12-01 00:00:00
abstract::Association studies are a potentially powerful approach to identifying susceptibility variants for common multifactorial diseases such as type 1 diabetes, but the results are not always consistently reproducible. The IDDM5 locus has recently been narrowed to an approximately 200-kb interval on chromosome 6q25 by two i...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3582
更新日期:2005-12-01 00:00:00
abstract::The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.300
更新日期:2003-02-01 00:00:00
abstract::To determine the role of the endoplasmic reticulum (ER) in diabetes, Akita mice, a mouse model of type 2 diabetes, were mated with either heterozygous knockout mice or two types of transgenic mice of 150-kDa oxygen-regulated protein (ORP150), a molecular chaperone located in the ER. Systemic expression of ORP150 in Ak...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.3.657
更新日期:2005-03-01 00:00:00
abstract::We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.3.398
更新日期:1993-03-01 00:00:00
abstract::Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon-gam...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.10.1174
更新日期:1986-10-01 00:00:00
abstract::Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) allevia...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0662
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0839
更新日期:2010-03-01 00:00:00
abstract::Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1119
更新日期:1992-09-01 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::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::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 an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1068
更新日期:2017-05-01 00:00:00
abstract::Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial f...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db14-0667
更新日期:2015-04-01 00:00:00
abstract::Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli wer...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.130
更新日期:1989-01-01 00:00:00
abstract::This study addressed the controversial question of whether a negative-insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.36.8.959
更新日期:1987-08-01 00:00:00
abstract::Analysis of conventional germ-line or tissue-specific gene manipulation in vivo is potentially confounded by developmental adaptation of animal physiology. We aimed to adapt the technique of in vivo electrotransfer (IVE) to alter local gene expression in skeletal muscle of rodents as a means of investigating the role ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.9.2702
更新日期:2005-09-01 00:00:00
abstract::The changes of the microvasculature of rat pancreas transplants during acute rejection were investigated and quantitatively analyzed. The vessels in pancreas transplants increased in caliber and decreased in density during acute rejection. These changes were marked in the exocrine pancreas, especially in central zones...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s111
更新日期:1989-01-01 00:00:00
abstract::PTPN22 encodes the lymphoid tyrosine phosphatase (LYP) and is the second strongest non-HLA genetic risk factor for type 1 diabetes. The PTPN22 susceptibility allele generates an LYP variant with an arginine-to-tryptophan substitution at position 620 (R620W) that has been reported by several studies to impart a gain of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0929
更新日期:2013-03-01 00:00:00
abstract::Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects wi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0234
更新日期:2016-11-01 00:00:00
abstract::Glucose-dependent insulinotropic peptide (GIP) is known to be degraded by dipeptidyl peptidase IV (DPP IV), forming an inactive metabolite, but the extent of the enzyme's role in regulating the biological activity of GIP in vivo is still largely unknown. In nonfasted anesthetized pigs given an intravenous infusion of ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.7.1588
更新日期:2001-07-01 00:00:00
abstract::Glucagon-like peptide 1 receptor (GLP-1R) imaging with radiolabeled exendin has proven to be a powerful tool to quantify β-cell mass (BCM) in vivo. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose (BG) levels on GLP-1R-mediated exendin uptake in both murine ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0616
更新日期:2020-11-01 00:00:00