Abstract:
:This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had significantly increased serum levels of free fatty acid and body fat. Despite no significant difference in placental weight, lipoprotein lipase (LPL) protein levels and activity were remarkably elevated in placentas from HF-fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3, FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although both peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α protein levels were significantly increased in placentas of the HF group, only PPARγ exhibited a stimulative effect on LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1 activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1 on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARγ expression in trophoblasts. Most importantly, inhibition of PPARγ abolished the SIRT1-mediated regulatory effect on LPL expression. Together, these results indicate that maternal overnutrition induces LPL expression in trophoblasts by reducing the inhibitory effect of SIRT1 on PPARγ.
journal_name
Diabetesjournal_title
Diabetesauthors
Qiao L,Guo Z,Bosco C,Guidotti S,Wang Y,Wang M,Parast M,Schaack J,Hay WW Jr,Moore TR,Shao Jdoi
10.2337/db14-1627subject
Has Abstractpub_date
2015-09-01 00:00:00pages
3111-20issue
9eissn
0012-1797issn
1939-327Xpii
db14-1627journal_volume
64pub_type
杂志文章相关文献
DIABETES文献大全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::In view of reports that accessory pathways of glucose oxidation are enhanced in the diabetic state, we have determined the levels of key enzymes of the glucuronate-xylulose cycle in the livers of diabetic mice and rats. Genetically diabetic mice (db/db) were found to have increased levels of two NADP-linked enzymes of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.9.793
更新日期:1979-09-01 00:00:00
abstract:OBJECTIVE:Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly understood....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0233
更新日期:2010-09-01 00:00:00
abstract::To explain the contradictory data on the secretion of prostacyclin (PGI2) in clinical and experimental diabetes, we have investigated the effect of each of the major metabolic abnormalities in uncontrolled diabetes on vascular PGI2 synthesis. An increase in fatty acid concentrations caused a dose-dependent inhibition ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.3.217
更新日期:1983-03-01 00:00:00
abstract::Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effect...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.10.1274
更新日期:1991-10-01 00:00:00
abstract::Decreased uncoupling protein (UCP)3 is associated with insulin resistance in muscle of pre-diabetic and diabetic individuals, but the function of UCP3 remains unclear. Our goal was to elucidate mechanisms underlying the negative correlation between UCP3 and insulin resistance in muscle. We determined effects of physio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.8.2343
更新日期:2005-08-01 00:00:00
abstract::Some of the actions of leptin depend on cholecystokinin (CCK). However, it is unknown whether leptin modulates the release of CCK. Here, we demonstrate in vitro that leptin induces the phosphorylation of extracellular signal-related kinase (ERK)-1/2 proteins and increases CCK release (EC(50) = 0.23 nmol/l) in CCK-secr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.7.1664
更新日期:2003-07-01 00:00:00
abstract::Impaired wound healing is one of the main causes of diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes is not fully understood. Long noncoding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complicati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0147
更新日期:2020-10-01 00:00:00
abstract::GAD autoantibodies (GADAs) are sensitive markers of islet autoimmunity and type 1 diabetes. They form the basis of robust prediction models and are widely used for the recruitment of subjects at high risk of type 1 diabetes to prevention trials. However, GADAs are also found in many individuals at low risk of diabetes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1693
更新日期:2015-09-01 00:00:00
abstract::The time course of islet cell antibodies (ICA) and serum C-peptides responses (CPRs) to oral glucose tolerance tests (OGTTs) were studied prospectively up to 60 (mean 35) mo in 32 ICA-positive subjects [28 with non-insulin-dependent diabetes (NIDDM) and 4 subjects with impaired glucose tolerance (IGT); mean age 45 yr]...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.4.510
更新日期:1987-04-01 00:00:00
abstract::Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8(+) T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0071
更新日期:2012-07-01 00:00:00
abstract::An A-to-G transition in the mitochondrial tRNALeu(UUR) gene at base pair 3243 has been shown to be associated with the maternally transmitted clinical phenotype of NIDDM and sensorineural hearing loss in white and Japanese pedigrees. We have detected this mutation in 25 of 50 tested members of five white French pedigr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.4.478
更新日期:1996-04-01 00:00:00
abstract::Although diabetes is the most common cause of end-stage renal disease (ESRD) worldwide, most people with diabetic nephropathy will never develop ESRD but will instead die of cardiovascular (CV) disease (CVD). The first evidence of kidney injury in diabetes is often microalbuminuria, itself also an independent risk mar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0795
更新日期:2013-11-01 00:00:00
abstract::Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising ini...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1212
更新日期:2015-04-01 00:00:00
abstract::To address the problem of the pathogenesis of diabetic neuropathy, rats were made diabetic by alloxan administration, and sciatic nerves were sampled for electrolyte and water content and levels of selected carbohydrates and intermediates in energy metabolism at 3, 6, and 26 weeks. Significant increases were seen in t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.2.190
更新日期:1995-02-01 00:00:00
abstract::We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2676
更新日期:2004-10-01 00:00:00
abstract::Cellular cholesterol homeostasis is important for normal β-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking β-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transpor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1341
更新日期:2012-03-01 00:00:00
abstract::Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (AT) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (NAFLD). Exosome components, liver fat conte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0146
更新日期:2021-02-01 00:00:00
abstract::Agonist-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) stimulates adipocyte differentiation and insulin sensitivity. Patients with heterozygous PPARγ dominant-negative mutation develop partial lipodystrophy and insulin resistance. Inconsistent with this evidence in humans, it was reported t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1422
更新日期:2016-10-01 00:00:00
abstract::GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD) mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to be associated with the development of autoimmune diabetes. Hormonal changes through environmental stimuli are considered to influence the expression of the d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.9.2764
更新日期:2002-09-01 00:00:00
abstract::Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process. Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secret...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0785
更新日期:2013-03-01 00:00:00
abstract::The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (app...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.8.965
更新日期:1990-08-01 00:00:00
abstract::Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this "glucose effectiveness" is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). KATP channels in the central nervous system have been shown to regulate EGP in humans and rodents. We examined the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-1256
更新日期:2020-06-01 00:00:00
abstract::Different degrees of beta-cell failure and apoptosis are present in type 1 and type 2 diabetes. It has been recently suggested that high glucose-induced beta-cell apoptosis in type 2 diabetes shares a final common pathway with type 1 diabetes, involving interleukin-1beta (IL-1beta) production by beta-cells, nuclear fa...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.11.3238
更新日期:2005-11-01 00:00:00
abstract::The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.9.1863
更新日期:1999-09-01 00:00:00
abstract::Exercise-induced hyperinsulinism (EIHI) is an autosomal dominant disorder characterized by inappropriate insulin secretion in response to vigorous physical exercise or pyruvate injection. Activating mutations in the monocarboxylate transporter-1 (MCT1, SLC16A1) promoter have been linked to EIHI. Expression of this pyr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1531
更新日期:2012-07-01 00:00:00
abstract::A genome scan for B10-derived loci that reduce the frequency of diabetes and insulitis in NOD mice demonstrated a large region (34 cM) of linkage on the proximal end of chromosome 1. This locus was designated Idd5 and encompassed candidate genes including Il1r1, Il1r2, Stat1, Stat4, Nramp1, and Bcl2. In the current st...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.10.1744
更新日期:2000-10-01 00:00:00
abstract::Antibodies to an islet protein of 64,000 Mr (64K antibodies) were measured in 15 diabetic children who were followed prospectively for up to 3 yr after onset of type I (insulin-dependent) diabetes. Of the 15 children, 12 were positive for 64K antibodies at diagnosis. Those patients who were negative for these antibodi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.6.653
更新日期:1990-06-01 00:00:00
abstract::Insulin and glucagon release and insulin sensitivity were investigated in patients with glucokinase deficiency. Five subjects with a missense mutation (Glu256Lys) were studied. They were compared with six healthy subjects with low insulin response but normal glucose tolerance. Insulin and glucagon levels were measured...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.12.1402
更新日期:1994-12-01 00:00:00
abstract::The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte globulin and etanercept induction, islet culture, heparinization, and intensive insulin therapy with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engraf...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1802
更新日期:2013-08-01 00:00:00