Abstract:
BACKGROUND:Previous works indicated that the stress on the endoplasmic reticulum (ER) affected nonalcoholic fatty liver disease (NAFLD). However, there is no clear evident on the effect of the regulation of ER stress by angiotensin-converting enzyme 2 (ACE2) on the prevention of NAFLD. METHODS:HepG2 cells were treated with thapsigargin (Tg) or palmitic acid (PA). We analysed ACE2 expression using Western-blotting analyses. ER stress-related proteins were detected in ACE2 knockout mice and Ad-ACE2-treated db/db mice by immunofluorescence or Western-blotting analyses. In ACE2-overexpression HepG2 cells, the triglyceride (TG), total cholesterol (TC), and glycogen content were detected by assay kits. Meanwhile, the expression of hepatic lipogenic proteins (ACCα, SREBP-1c, FAS, and LXRα), enzymes for gluconeogenesis (PEPCK, G6Pase, and IRS2), and IKKβ/NFκB/IRS1/Akt pathway were analysed by Western-blotting analyses. RESULTS:ACE2 was significantly increased in Tg/PA-induced cultured hepatocytes. Additionally, ACE2 knockout mice displayed elevated levels of ER stress, while Ad-ACE2-treated db/db mice showed reduced ER stress in liver. Furthermore, activation of ACE2 can ameliorate ER stress, accompanied by decreased TG content, increased intracellular glycogen, and downregulated expression of hepatic lipogenic proteins and enzymes for gluconeogenesis in Tg/PA-induced hepatocytes. As a consequence of anti-ER stress, the activation of ACE2 led to improved glucose and lipid metabolism through the IKKβ/NFκB/IRS1/Akt pathway. CONCLUSIONS:This is the first time documented that ACE2 had a notable alleviating role in ER stress-induced hepatic steatosis and glucose metabolism via the IKKβ/NFκB/IRS1/Akt-mediated pathway. This study may further provide insight into a novel underlying mechanism and a strategy for treating NAFLD.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Cao X,Song LN,Zhang YC,Li Q,Shi TT,Yang FY,Yuan MX,Xin Z,Yang JKdoi
10.1002/dmrr.3123subject
Has Abstractpub_date
2019-05-01 00:00:00pages
e3123issue
4eissn
1520-7552issn
1520-7560journal_volume
35pub_type
杂志文章abstract:BACKGROUND:To evaluate possible differences in distal polyneuropathy (PN) characteristics and degree of abnormalities for various small and large fibre parameters in diabetes type 1 (DM1) and type 2 (DM2). METHODS:Sixty-six DM1 and 57 DM2 patients with or without PN symptoms were included. Nerve conduction studies (NC...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.1049
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. METHODS:The 5-methylcytosine content was assessed by reversed-phase ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2584
更新日期:2015-02-01 00:00:00
abstract:OBJECTIVE:To investigate the relationship between ankle-branchial index (ABI) and cardiovascular disease in type 2 diabetes patients. METHODS:A total of 634 inpatients with type 2 diabetes were recruited in this cross-sectional study. All patients were measured with ABI and computed tomography angiography (CTA) scan f...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3076
更新日期:2019-01-01 00:00:00
abstract::Cardiorespiratory fitness, which is determined mainly by the level of physical activity, is inversely related to mortality in the general population as well as in subjects with diabetes, the incidence of which is also increased by low exercise capacity. Exercise is capable of promoting glucose utilization in normal su...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.982
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Elevated liver enzymes are associated with cardiovascular disease, while their relationship with cancer-related mortality has not been assessed so far in diabetic patients. METHODS:An observational cohort study was performed on a consecutive series of 1952 type 2 diabetic patients. The association of liver ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.744
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:HLA region is the major locus (IDDM1) of type 1 diabetes (T1D) susceptibility. It explains approximately 50% of the genetic background of T1D, indicating additional genetic determinants. Genome scans and candidate gene studies have generated several chromosomal candidate regions that may have a role in T1D d...
journal_title:Diabetes/metabolism research and reviews
pub_type: 临床试验,杂志文章
doi:10.1002/dmrr.424
更新日期:2004-03-01 00:00:00
abstract::Hepatic glycogen is replenished during the absorptive period postprandially. This repletion is prompted partly by an increased hepatic uptake of glucose by the liver, partly by metabolite and hormonal signals in the portal vein, and partly by an increased gluconeogenic flux to glycogen (glyconeogenesis). There is some...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.217
更新日期:2001-07-01 00:00:00
abstract::Hypoglycaemia is inevitable when striving for low HbA1c values. Nocturnal hypoglycaemia often occurs without symptoms, but results in diminished next day well-being and hypoglycaemia unawareness. Frequency of nocturnal hypoglycaemia was first assessed in research ward settings, but suffered from insufficient glucose s...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.513
更新日期:2004-11-01 00:00:00
abstract::Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be hi...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.1068
更新日期:2010-03-01 00:00:00
abstract::Small fibres constitute 70-90% of peripheral nerve fibres and regulate several key functions such as tissue blood flow, temperature and pain perception as well as sweating, all of which are highly relevant to the clinical presentation and adverse outcomes associated with foot ulcerations in patients with diabetes. Rec...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,实务指引
doi:10.1002/dmrr.1222
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:We aimed to predict the incidence of obesity in a Korean population using a genetic risk score (GRS) constructed with obesity-related single nucleotide polymorphisms (SNPs) along with an oxidative stress score (OSS). METHODS:A total of 9460 Korean subjects and 356 974 SNPs were included. The GRS was constru...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3230
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Lispro Mix 25% insulin lispro/75% insulin lispro protamine (LM25) and Lispro Mix 50% insulin lispro/50% insulin lispro protamine (LM50) were compared as starter insulins in East Asian patients with type 2 diabetes. METHODS:Phase 4, open-label, randomized trial conducted in China, Japan, Korea, and Turkey. S...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/dmrr.2816
更新日期:2017-01-01 00:00:00
abstract::A few studies have investigated the relationship between type 1 diabetes mellitus (T1DM) and bone mineral density (BMD) values. This meta-analysis was performed to explore differences between T1DM and healthy individuals in BMD values measured at five bone sites.We searched the database of PubMed for cross-sectional s...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/dmrr.2508
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Cardiac hypertrophy is a key structural feature of diabetic cardiomyopathy. Previous studies have shown that diabetes-induced endothelin-1 (ET-1) and sodium hydrogen exchanger-1 (NHE-1) mediate structural and functional deficits in the heart. In order to gain a mechanistic understanding of the role of ET-1 a...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.689
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Patients with impaired 50-g oral glucose challenge test (OGCT) have not been investigated for fetal anterior abdominal wall thickness until now. We aimed to investigate patients with impaired 50-g OGCT, but not gestational diabetes and match them with healthy uneventful pregnant participants for anterior abd...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2511
更新日期:2014-10-01 00:00:00
abstract::Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experien...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/dmrr.2470
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Human leukocyte antigen (HLA) genotypes associated with increased risk for type 1 diabetes mellitus (T1D) have been reported to be associated with increased birth weight. We set out to investigate the association between HLA haplotypes conferring risk for T1D and birth weight and search for possible differen...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,多中心研究
doi:10.1002/dmrr.2303
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) can lead to cirrhosis and hepatocellular carcinoma and is strongly associated with obesity and insulin resistance. The aim of this study was to assess if plasma markers associated with NAFLD are increased in people with concomitant diabetes compared with those withou...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2269
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Our previous studies showed that some Korean type 2 diabetic patients could maintain long-term normal blood glucose control without any medication, referred to as remission after a certain period of normalization of blood glucose level by continuous subcutaneous insulin infusion (CSII) treatment. In this stu...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.343
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Adenosine triphosphate (ATP) is a critical determinant of beta-cell insulin secretion in response to glucose. BHE/cdb rats have a mutation in ATP synthase that limits ATP production, yet develop mild diabetes only with ageing. We investigated the cellular basis for reduced insulin secretion and compensatory ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.819
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well-defined, only limited information is available on alpha cells. This study evaluates the long-term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation. METHODS:Cl...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.663
更新日期:2007-03-01 00:00:00
abstract::The use of endovascular therapy (EVT) for lower extremity atherosclerosis is markedly increasing while open surgical bypass is in decline. The results of EVT for critical limb ischaemia (CLI) are difficult to evaluate, especially for patients with diabetes. To date, only one randomized, prospective trial has been publ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.829
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta-analysis of the use of NA in patients with recent-onset Type 1 diabetes. METHODS:...
journal_title:Diabetes/metabolism research and reviews
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/(sici)1520-7560(199905/06)15:3<181::aid-dm
更新日期:1999-05-01 00:00:00
abstract::Hypertension is a major modifiable risk factor for cardiovascular morbidity and mortality in diabetic patients. Guidelines recommend lowering blood pressure (BP) to less than 130/80 mmHg in diabetic patients. These recommendations are based on several studies in diabetic patients that showed the benefit of intensive B...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.2348
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Diabetes mellitus is an endocrine disorder which is characterized by the development of resistance to the cellular activity of insulin or inadequate insulin production. It leads to hyperglycemia, prolonged inflammation, and oxidative stress. Oxidative stress is assumed to play an important role in the develo...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3060
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Levels of high-sensitivity C-reactive protein (hs-CRP) and adiponectin, reflecting chronic inflammation, are associated with cardiovascular disease in type 2 diabetes. The long-term effects of multifactorial therapy in type 2 diabetes patients on CRP and adiponectin are unknown. METHODS:The ADDITION-NL stud...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,随机对照试验
doi:10.1002/dmrr.2669
更新日期:2015-10-01 00:00:00
abstract::This review addresses the roles of Rho/Rho-kinase (ROCK) pathway in the pathogenesis of diabetes complications. Diabetes can cause many serious complications and can result in physical disability or even increased mortality. However, there are not many effective ways to treat these complications. The small guanosine-5...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.1182
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Clinical and experimental studies have shown that a reduction in myocardial glucose utilization is a factor contributing to diabetic cardiomyopathy. This study determined whether exercise training could prevent the depression in glucose utilization observed in the diabetic rat heart. METHODS:Diabetes was in...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.479
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:ZAC (Zinc finger protein that regulates apoptosis and cell-cycle arrest) is a candidate gene for transient neonatal diabetes mellitus (TNDM). This condition involves severe insulin deficiency at birth that reverses over weeks or months but may relapse with diabetes recurring in later life. ZAC overexpression...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2325
更新日期:2012-11-01 00:00:00
abstract::A recent study from Gallagher et al. aimed to investigate the effect of a new depeptidyl-peptidase-4 inhibitor, MK-0626, on bone turnover in a mouse model developing insulin resistance and diabetes (MKR mice). Authors have found that treatment with MK-0626 did not affect either MKR mice fasting glucose or parameters o...
journal_title:Diabetes/metabolism research and reviews
pub_type: 评论,杂志文章
doi:10.1002/dmrr.2505
更新日期:2014-03-01 00:00:00