Abstract：
AIMS/HYPOTHESIS:The effect of renin inhibition on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of aliskiren, a direct renin inhibitor, on cardiovascular injuries, glucose intolerance and pancreatic injury in a mouse model of type 2 diabetes. METHODS:Groups of db/db mice, with obesity and type 2 diabetes, were treated with aliskiren (3, 6, 12 and 25 mg kg(-1) day(-1)) or hydralazine (80 mg kg(-1) day(-1)) for 6 weeks, and the protective effects were extensively compared among groups. RESULTS:All sub-pressor and hypotensive doses of aliskiren significantly attenuated cardiac fibrosis, macrophage infiltration and coronary remodelling, and improved vascular endothelial function in db/db mice. These protective effects of aliskiren were attributed to the attenuation of cardiac p22(phox)-related NADPH oxidase-induced superoxide and the restoration of vascular endothelial nitric oxide synthase (eNOS) production. Aliskiren at the highest dose (25 mg kg(-1) day(-1)), but not at lower doses, partially reduced glucose intolerance in db/db mice. Furthermore, the highest dose of aliskiren significantly attenuated the decreases in pancreatic islet insulin content and beta cell mass, and prevented pancreatic islet fibrosis in db/db mice, being associated with the reduction of 8-hydroxy-2'-deoxyguanosine-positive cells and Nox2 (also known as Cybb) expression in pancreatic islets by aliskiren. CONCLUSIONS/INTERPRETATION:Our work provides the first evidence that direct renin inhibition with aliskiren protects against cardiovascular complications and pancreatic injury, through the attenuation of oxidative stress. Thus, we propose that aliskiren may be a promising therapeutic agent for type 2 diabetes.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Dong YF,Liu L,Kataoka K,Nakamura T,Fukuda M,Tokutomi Y,Nako H,Ogawa H,Kim-Mitsuyama Sdoi
10.1007/s00125-009-1575-5subject
Has Abstractpub_date
2010-01-01 00:00:00pages
180-91issue
1eissn
0012-186Xissn
1432-0428journal_volume
53pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract：AIMS/HYPOTHESIS:Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaem...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-015-3636-2
更新日期：2015-08-01 00:00:00
abstract：:The ability of the amino acid leucine and its keto acid, alpha-ketoisocaproate, to induce insulin release, to initiate phosphoinositide hydrolysis, and to amplify the subsequent insulin secretory response to glucose was assessed. In islets whose inositol-containing lipids were prelabelled with myo[2-3H]inositol, the a...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00271588
更新日期：1988-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:Mitochondria-associated endoplasmic reticulum membranes (MAMs) are regions of the endoplasmic reticulum (ER) tethered to mitochondria and controlling calcium (Ca(2+)) transfer between both organelles through the complex formed between the voltage-dependent anion channel, glucose-regulated protein 75 and...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-015-3829-8
更新日期：2016-03-01 00:00:00
abstract：:The in vivo radioautographic method has been applied to elucidate the mechanism of direct peptide hormone "feedback" action in the CNS. Using this method we have identified the circumventricular organs of the brain as general endocrine target tissues for a variety of blood-borne polypeptide hormones, including insulin...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00254491
更新日期：1981-03-01 00:00:00
abstract：:The characteristics of familial Type I (insulin-dependent) diabetes mellitus-that is Type I diabetes in a first degree relative were investigated for children diagnosed before the age of 15 years using data from an international network of population-based registries (the EURODIAB ACE network) and from a case-control ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051044
更新日期：1998-10-01 00:00:00
abstract：AIMS/HYPOTHESIS:We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat r...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-004-1600-7
更新日期：2005-01-01 00:00:00
abstract：:Using an antiserum raised to a recombinant coxsackie virus B 3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and panc...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00403323
更新日期：1990-05-01 00:00:00
abstract：:The response of Gastric Inhibitory Polypeptide (GIP) and insulin to a 50 g oral glucose tolerance test (OGTT) and an intravenous glucose infusion (IVGI), which copied the changes in plasma glucose concentrations during the OGTT, were measured in 10 patients with duodenal ulcer and in 10 healthy control subjects. The m...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00429773
更新日期：1978-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. METHODS:We studied 2,603 and 2,386 Europeans from the Botnia study and Malmö Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-u...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-014-3390-x
更新日期：2015-01-01 00:00:00
abstract：:We have studied the epidemiologic characteristics of insulin-dependent (Type 1) diabetic patients aged 0-19 in a city (San Diego, southern California, USA) characterized by an impressive racial diversity and especially mild and constant climatic conditions. Ascertainment was through retrospective review of medical rec...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00265020
更新日期：1985-10-01 00:00:00
abstract：:The aims of this survey were (1) to estimate the prevalence of known diabetes mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different data sources available in Italy; (3) to identify a population-based cohort of diabetic patients. Multiple independent data sources were used and the capture-re...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00399931
更新日期：1992-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:The AERx insulin Diabetes Management system (AERx iDMS) is a liquid aerosol device that enables insulin to be administered to the peripheral parts of the lung. This study aimed to compare the pharmacokinetic and pharmacodynamic properties of insulin which is inhaled using AERx iDMS with insulin which is...
journal_title：Diabetologia
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s001250051618
更新日期：2001-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:Diabetes increases the risk of premature death and reduces work productivity. We estimated the impact of diabetes in China in terms of mortality, years of life lost, and productivity-adjusted life years (PALYs) lost in the Chinese population. METHODS:Life table modelling was used with simulated follow-...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-019-4875-4
更新日期：2019-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insuli...
journal_title：Diabetologia
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s00125-004-1421-8
更新日期：2004-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:Microvascular endothelial hyperpermeability, mainly caused by claudin-5 deficiency, is the initial pathological change that occurs in diabetes-associated cardiovascular disease. The ketone body β-hydroxybutyrate (BHB) exerts unique beneficial effects on the cardiovascular system, but the involvement of ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-020-05305-2
更新日期：2021-01-01 00:00:00
abstract：AIMS/HYPOTHESIS:Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (T(h)1) response, mainly represented by Ig...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-004-1558-5
更新日期：2004-11-01 00:00:00
abstract：AIMS/HYPOTHESIS:Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-012-2674-2
更新日期：2012-11-01 00:00:00
abstract：:Non-insulin adjunct therapies in type 1 diabetes have been proposed as a means of improving glycaemic control and reducing risk of hypoglycaemia. Evidence to support this approach is, however, scant and few pharmacological agents have proved effective enough to become part of routine clinical care. Recent short-term P...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-018-4671-6
更新日期：2018-10-01 00:00:00
abstract：:The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional ass...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00274531
更新日期：1989-10-01 00:00:00
abstract：:Using a prospective randomised double-blind crossover design, the effect of the angiotensin converting enzyme inhibitor enalapril compared to a placebo was studied in 18 normotensive, normoalbuminuric Type 1 (insulin-dependent) diabetic children. Each patient had a high normal or clearly elevated glomerular filtration...
journal_title：Diabetologia
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00285294
更新日期：1989-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:High intake of carbohydrates, particularly sucrose, in western societies is associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related primarily to the carbohydrate quantity or to the hormonal responses, particularly glucose-dependent...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-014-3423-5
更新日期：2015-02-01 00:00:00
abstract：:This study aimed at evaluating the influence of furosemide upon insulin and glucagon responses to arginine in healthy subjects. For this purpose, six normal subjects received two consecutive arginine pulses (3 g), 60 min apart, before and after the administration of furosemide (40 mg, IV). The acute insulin response (...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00251008
更新日期：1980-04-01 00:00:00
abstract：:Closure of ATP-regulated K(+) channels (K(ATP) channels) plays a central role in glucose-stimulated insulin secretion in beta cells. K(ATP) channels are also highly expressed in glucagon-producing alpha cells, where their function remains unresolved. Under hypoglycaemic conditions, K(ATP) channels are open in alpha ce...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-014-3279-8
更新日期：2014-09-01 00:00:00
abstract：:AMP-activated protein kinase (AMPK) serves as a major regulator of energy homeostasis and is activated by different glucose-lowering agents. Indeed, AMPK has been identified as an attractive target for the development of innovative molecules to treat type 2 diabetes. In this issue of Diabetologia (doi: ...
journal_title：Diabetologia
pub_type： 评论,杂志文章
doi：10.1007/s00125-012-2503-7
更新日期：2012-05-01 00:00:00
abstract：AIMS/HYPOTHESIS:Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as 'maturity-onset diabetes of the young'. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive i...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-008-0942-y
更新日期：2008-04-01 00:00:00
abstract：:The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle glycogen storage and gl...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00428782
更新日期：1994-01-01 00:00:00
abstract：:Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00401372
更新日期：1992-12-01 00:00:00
abstract：:The NOD mouse, which shows many features of human IDDM, is extensively used to evaluate the role of T lymphocytes in the pathogenesis of autoimmune diabetes. The development of diabetes in this model appears to be controlled by a finely tuned immunoregulatory balance between autoaggressive T cells and regulatory immun...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00408468
更新日期：1994-04-01 00:00:00
abstract：:Non-insulin-dependent diabetic (NIDDM) patients were studied during a modified euglycaemic state when fasting hyperglycaemia was normalized by a prior (-210 to -150 min)--and later withdrawn (-150-0 min)--intravenous insulin infusion. Glucose metabolism was assessed in NIDDM patients (n = 10) and matched control subje...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00400638
更新日期：1995-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:Experimental studies have suggested that ghrelin, a novel gastrointestinal peptide hormone, could play a role in glucose homeostasis. In addition, ghrelin has been associated with beneficial haemodynamic effects in experimental settings. Since the Arg51Gln mutation changes the carboxyterminal amino acid...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-003-1058-z
更新日期：2003-04-01 00:00:00
