Abstract:
:Women gain weight and their diabetes risk increases as they transition through menopause; these changes can be partly reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen receptor (ER) pathway was used, and we found that the lack of this pathway precipitated excessive weight gain and glucose intolerance independent of food intake and that this was accompanied by impaired adaptive thermogenesis and reduced physical activity. Notably, the central activation of protein phosphatase (PP) 2A improved metabolic disorders induced by the lack of membrane-initiated ER signaling. Furthermore, the antiobesity effect of estrogen replacement in a murine menopause model was abolished by central PP2A inactivation. These findings define a critical role for membrane-initiated ER signaling in metabolic homeostasis via the central action of PP2A.
journal_name
Diabetesjournal_title
Diabetesauthors
Ueda K,Takimoto E,Lu Q,Liu P,Fukuma N,Adachi Y,Suzuki R,Chou S,Baur W,Aronovitz MJ,Greenberg AS,Komuro I,Karas RHdoi
10.2337/db17-1342subject
Has Abstractpub_date
2018-08-01 00:00:00pages
1524-1537issue
8eissn
0012-1797issn
1939-327Xpii
db17-1342journal_volume
67pub_type
杂志文章相关文献
DIABETES文献大全abstract::Marked improvement in glycemic control occurs in patients with type 2 diabetes mellitus shortly after Roux-en-Y gastric bypass surgery (RYGB) and before there is major weight loss. The objective of this study was to determine whether the magnitude of this change is primarily due to caloric restriction or is unique to ...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db12-1762
更新日期:2013-09-01 00:00:00
abstract::A new murine model of porcine islet-like cell cluster (ICC) xenograft rejection, avoiding interference of unspecific inflammation, was introduced and used to investigate rejection mechanisms. Athymic (nu/nu) mice were transplanted with syngeneic, allogeneic, or xenogeneic islets under the kidney capsule. After the ori...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.5.1111
更新日期:2003-05-01 00:00:00
abstract::The contribution of dietary amino acids and endogenous hyperinsulinemia to prandial protein anabolism still has not been established. To this end, leucine estimates ([1-14C]leucine infusion, plasma alpha-ketoisocaproic acid [KIC] specific activity [SA] as precursor pool SA) of whole-body protein kinetics and fractiona...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.9.1245
更新日期:1996-09-01 00:00:00
abstract::Insulin antagonism characterizes infection, but the mechanism is unknown. Previous studies have been performed during the acute catabolic stage of infection, and the resultant metabolic changes reflect this decreased food intake and weight loss. To delineate metabolic alterations due to infection itself, rats with pye...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.10.881
更新日期:1975-10-01 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:OBJECTIVE:Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), now known as G6PC2, is a major target of autoreactive T cells implicated in the pathogenesis of type 1 diabetes in both mice and humans. This study aimed to determine whether suppression of G6p2 gene expression might therefore prev...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0220
更新日期:2011-11-01 00:00:00
abstract::The virtually fatless A-ZIP/F-1 mouse is profoundly insulin resistant, diabetic, and a good model for humans with severe generalized lipoatrophy. Like a number of other mouse models of diabetes, the A-ZIP/F-1 mouse has elevated serum corticosterone levels. Leptin infusion lowers the corticosterone levels, suggesting t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.7.2113
更新日期:2002-07-01 00:00:00
abstract::There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypep...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.663
更新日期:2004-03-01 00:00:00
abstract::Glucose homeostasis, a defining characteristic of physiological glucose metabolism, is the result of complex feedback relationships with both genetic and environmental determinants that influence insulin sensitivity and beta-cell function. Relatively little is known about the genetic basis of glucose homeostasis pheno...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/diabetes.55.04.06.db05-0813
更新日期:2006-04-01 00:00:00
abstract::Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the p...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db05-1685
更新日期:2006-05-01 00:00:00
abstract::Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.1.133
更新日期:2005-01-01 00:00:00
abstract::A chronic diabetic state was produced in Macaca fuscatus , and these diabetic monkeys were kept without insulin treatment for up to 25 mo. The metabolic derangements were characterized by hyperglycemia, insulinopenia, hyperglucagonemia, ketonemia, and hyperlipidemia. Significant thickening of the capillary basement me...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.5.415
更新日期:1984-05-01 00:00:00
abstract::Culture of mesangial cells (MCs) in 5.6 vs. 30.0 mmol/l glucose for 3 weeks induced a sustained increase in protein kinase C (PKC) activity, transforming growth factor (TGF)-beta1 mRNA, bioactive TGF-beta, and collagen synthesis. Nitric oxide (NO), generated exogenously by the NO donor S-nitroso-N-acetyl, D,L-penicill...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.4.671
更新日期:1997-04-01 00:00:00
abstract::Enhanced advanced glycosylation end product (AGE) formation has been shown to participate in the pathogenesis of diabetes-induced glomerular injury by mediating the increased extracellular matrix (ECM) deposition and altered cell growth and turnover leading to mesangial expansion. These effects could be exerted via an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.11.1881
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVE:To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes. RESEARCH DESIGN AND METHO...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0263
更新日期:2011-11-01 00:00:00
abstract::Diabetic nephropathy is the main cause of end-stage renal disease requiring dialysis in developed countries. In this study, we demonstrated the therapeutic effect of hepatocyte growth factor (HGF) on advanced rather than early diabetic nephropathy using a rat model of streptozotocin-induced diabetes. Early diabetic ne...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.4.1119
更新日期:2004-04-01 00:00:00
abstract::The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.1.6
更新日期:1992-01-01 00:00:00
abstract::beta-Cell cycle progression and proliferation are critical to maintain beta-cell mass in adult mice. Of the cell cycle inhibitors, p27Kip1 is thought to be the primary modulator of the proliferative status in most cell types. p27 plays a role in beta-cell adaptation in genetic models of insulin resistance. To study th...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0861
更新日期:2006-12-01 00:00:00
abstract::Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ~50% of these neurons responded to oleic acid (OA) by using the FA t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1689
更新日期:2013-08-01 00:00:00
abstract::The flavonoid naringenin improves hyperlipidemia and hyperglycemia in streptozotocin-treated rats. In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.10.2554
更新日期:2003-10-01 00:00:00
abstract::Pancreatic β-cell ATP-sensitive K(+) (K(ATP)) channels are composed of Kir6.2 and SUR1 subunits encoded by the KCNJ11 and ABCC8 genes, respectively. Although rare monogenic activating mutations in these genes cause overt neonatal diabetes, the common variants E23K (KCNJ11) and S1369A (ABCC8) form a tightly heritable h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0371
更新日期:2012-01-01 00:00:00
abstract::The Dio2 gene encodes the type 2 deiodinase (D2) that activates thyroxine (T4) to 3,3',5-triiodothyronine (T3), the disruption of which (Dio2(-/-)) results in brown adipose tissue (BAT)-specific hypothyroidism in an otherwise euthyroid animal. In the present studies, cold exposure increased Dio2(-/-) BAT sympathetic s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.577
更新日期:2004-03-01 00:00:00
abstract::Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase β-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the phys...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1013
更新日期:2013-05-01 00:00:00
abstract::Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 ob...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db15-0675
更新日期:2016-01-01 00:00:00
abstract::The effect of Ca2+ and calmodulin has been studied on adenylate cyclase activity in homogenates of rat islets of Langerhans. EGTA had a stimulatory effect on the enzyme in accord with the known inhibitory effect of Ca2+. In contrast, the addition of Ca2+ together with calmodulin is stimulatory and demonstrates the exi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.1.74
更新日期:1980-01-01 00:00:00
abstract::Recent work suggests that insulin may exert both positive and negative feedback directly on pancreatic beta-cells. To investigate the hypothesis that insulin modulates beta-cell metabolism, mouse islets and beta-cell clusters were loaded with rhodamine 123 to dynamically monitor mitochondrial membrane potential (Delta...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.7.1765
更新日期:2004-07-01 00:00:00
abstract::Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is down...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.03.06.db05-1075
更新日期:2006-03-01 00:00:00
abstract::Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cult...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diacare.46.10.1627
更新日期:1997-10-01 00:00:00
abstract::The effects of variations of glycemia from 1.7 to 35 mM on the activity of glycogen synthase and phosphorylase, on glycogen content, and on U-14C-glucose incorporation into glycogen in the liver of the near-term rat fetus were investigated. Hypoglycemia did not affect the activities of phosphorylase and synthase; tota...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.4.266
更新日期:1980-04-01 00:00:00
abstract::Polyalkylcyanoacrylate nanocapsules (mean size 220 nm), composed of spheric polymeric structures, have been used as a drug carrier for insulin. The rate of encapsulation of insulin is 54.9%, and we studied the therapeutic efficiency of the nanocapsules in diabetic and normal rats. When administered subcutaneously, ins...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.2.246
更新日期:1988-02-01 00:00:00