Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity.

Abstract:

:Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). 11betaHSD1 activates GCs, while 11betaHSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11betaHSD1 produces visceral obesity and the metabolic syndrome in mice. To determine whether adipocyte-specific inactivation of GCs protects against this phenotype, we created a transgenic model in which human 11betaHSD2 is expressed under the control of the murine adipocyte fatty acid binding protein (aP2) promoter (aP2-h11betaHSD2). Transgenic mice have increased 11betaHSD2 expression and activity exclusively in adipose tissue, with the highest levels in subcutaneous adipose tissue, while systemic indexes of GC exposure are unchanged. Transgenic mice resist weight gain on high-fat diet due to reduced fat mass accumulation. This improved energy balance is associated with decreased food intake, increased energy expenditure, and improved glucose tolerance and insulin sensitivity. Adipose tissue gene expression in transgenic mice is characterized by decreased expression of leptin and resistin and increased expression of adiponectin, peroxisome proliferator-activated receptor gamma, and uncoupling protein 2. These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome.

journal_name

Diabetes

journal_title

Diabetes

authors

Kershaw EE,Morton NM,Dhillon H,Ramage L,Seckl JR,Flier JS

doi

10.2337/diabetes.54.4.1023

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

1023-31

issue

4

eissn

0012-1797

issn

1939-327X

pii

54/4/1023

journal_volume

54

pub_type

杂志文章

相关文献

DIABETES文献大全
  • 3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism.

    abstract::Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and estab...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-1174

    authors: Nilsen MS,Jersin RÅ,Ulvik A,Madsen A,McCann A,Svensson PA,Svensson MK,Nedrebø BG,Gudbrandsen OA,Tell GS,Kahn CR,Ueland PM,Mellgren G,Dankel SN

    更新日期:2020-09-01 00:00:00

  • Mechanisms of control of the free Ca2+ concentration in the endoplasmic reticulum of mouse pancreatic β-cells: interplay with cell metabolism and [Ca2+]c and role of SERCA2b and SERCA3.

    abstract:OBJECTIVE:Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump Ca(2+) in the endoplasmic reticulum (ER) of pancreatic β-cells. We studied their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and the role of SERCA3 in the control of insulin secretion and ER stress. RESEARCH DES...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-1543

    authors: Ravier MA,Daro D,Roma LP,Jonas JC,Cheng-Xue R,Schuit FC,Gilon P

    更新日期:2011-10-01 00:00:00

  • Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation.

    abstract:OBJECTIVE:Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. RESEARCH DESIGN AND METHODS:Forearm skeletal musc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0857

    authors: Jocken JW,Roepstorff C,Goossens GH,van der Baan P,van Baak M,Saris WH,Kiens B,Blaak EE

    更新日期:2008-07-01 00:00:00

  • Progression to type 2 diabetes characterized by moderate then rapid glucose increases.

    abstract:OBJECTIVE:The transition of an individual from normoglycemia to diabetes has generally been thought to involve either moderate or rapid changes in glucose over time, although few studies have analyzed these changes. We sought to determine whether a general pattern of glucose change exists in most individuals who become...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0053

    authors: Mason CC,Hanson RL,Knowler WC

    更新日期:2007-08-01 00:00:00

  • Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes.

    abstract:OBJECTIVE:We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes-associated variants in the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), ADAMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0436

    authors: Grarup N,Andersen G,Krarup NT,Albrechtsen A,Schmitz O,Jørgensen T,Borch-Johnsen K,Hansen T,Pedersen O

    更新日期:2008-09-01 00:00:00

  • New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.

    abstract::We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IR...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.8.1949

    authors: Wang H,Rissanen J,Miettinen R,Kärkkäinen P,Kekäläinen P,Kuusisto J,Mykkänen L,Karhapää P,Laakso M

    更新日期:2001-08-01 00:00:00

  • Patients with chronic pancreatitis have islet progenitor cells in their ducts, but reversal of overt diabetes in NOD mice by anti-CD3 shows no evidence for islet regeneration.

    abstract::Monoclonal antibodies to T-cell coreceptors have been shown to tolerise autoreactive T-cells and prevent or even reverse autoimmune pathology. In type 1 diabetes, there is a loss of insulin-secreting beta-cells, and a cure for type 1 diabetes would require not only tolerance induction but also recovery of the function...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0832

    authors: Phillips JM,O'Reilly L,Bland C,Foulis AK,Cooke A

    更新日期:2007-03-01 00:00:00

  • The newly inbred cohen diabetic rat: a nonobese normolipidemic genetic model of diet-induced type 2 diabetes expressing sex differences.

    abstract::The newly inbred Cohen diabetic rat is an exceptional experimental model of diet-induced type 2 diabetes mellitus that is the result of secondary inbreeding nearly 30 years after it originally had been established. Animals from the original colony were selectively inbred by stringent criteria for 10 additional generat...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.11.2521

    authors: Weksler-Zangen S,Yagil C,Zangen DH,Ornoy A,Jacob HJ,Yagil Y

    更新日期:2001-11-01 00:00:00

  • Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat.

    abstract::Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/wee...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.12.2154

    authors: Hevener AL,Reichart D,Olefsky J

    更新日期:2000-12-01 00:00:00

  • Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

    abstract::One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increase...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1601

    authors: Pi J,Bai Y,Zhang Q,Wong V,Floering LM,Daniel K,Reece JM,Deeney JT,Andersen ME,Corkey BE,Collins S

    更新日期:2007-07-01 00:00:00

  • Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

    abstract::A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian B...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.837

    authors: Poulsen PL,Ebbehøj E,Arildsen H,Knudsen ST,Hansen KW,Mølgaard H,Mogensen CE

    更新日期:2001-04-01 00:00:00

  • Functional redundancy of CXCR3/CXCL10 signaling in the recruitment of diabetogenic cytotoxic T lymphocytes to pancreatic islets in a virally induced autoimmune diabetes model.

    abstract::Cytotoxic T lymphocytes (CTLs) constitute a major effector population in pancreatic islets from patients suffering from type 1 diabetes (T1D) and thus represent attractive targets for intervention. Some studies have suggested that blocking the interaction between the chemokine CXCL10 and its receptor CXCR3 on activate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-1370

    authors: Coppieters KT,Amirian N,Pagni PP,Baca Jones C,Wiberg A,Lasch S,Hintermann E,Christen U,von Herrath MG

    更新日期:2013-07-01 00:00:00

  • Proinsulin Expression Shapes the TCR Repertoire but Fails to Control the Development of Low-Avidity Insulin-Reactive CD8+ T Cells.

    abstract::NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8(+) T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/T...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1498

    authors: Pearson JA,Thayer TC,McLaren JE,Ladell K,De Leenheer E,Phillips A,Davies J,Kakabadse D,Miners K,Morgan P,Wen L,Price DA,Wong FS

    更新日期:2016-06-01 00:00:00

  • Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes.

    abstract::Oleanolic acid (OA), a natural component of many plant food and medicinal herbs, is endowed with a wide range of pharmacological properties whose therapeutic potential has only partly been exploited until now. Throughout complex and multifactorial mechanisms, OA exerts beneficial effects against diabetes and metabolic...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/db12-1215

    authors: Castellano JM,Guinda A,Delgado T,Rada M,Cayuela JA

    更新日期:2013-06-01 00:00:00

  • Association of glomerulopathy with the 5'-end polymorphism of the aldose reductase gene and renal insufficiency in type 2 diabetic patients.

    abstract::The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.11.2984

    authors: Zhao HL,Tong PC,Lai FM,Tomlinson B,Chan JC

    更新日期:2004-11-01 00:00:00

  • Hyperglycemia suppresses the adrenal medullary response to hypoxemia.

    abstract::An in vivo microdialysis technique was used to study adrenal medullary function in 6 euglycemic and 6 hyperglycemic anesthetized Sprague-Dawley rats exposed to hypoxia. After stabilization of an adrenal dialysis probe, dialyzable adrenal epinephrine and norepinephrine were measured in response to 15 min of 7.8% oxygen...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.5.645

    authors: Cohen WR,Deutsch J

    更新日期:1994-05-01 00:00:00

  • Klotho depletion contributes to increased inflammation in kidney of the db/db mouse model of diabetes via RelA (serine)536 phosphorylation.

    abstract:OBJECTIVE:Klotho is an antiaging hormone present in the kidney that extends the lifespan, regulates kidney function, and modulates cellular responses to oxidative stress. We investigated whether Klotho levels and signaling modulate inflammation in diabetic kidneys. RESEARCH DESIGN AND METHODS:Renal Klotho expression w...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-1262

    authors: Zhao Y,Banerjee S,Dey N,LeJeune WS,Sarkar PS,Brobey R,Rosenblatt KP,Tilton RG,Choudhary S

    更新日期:2011-07-01 00:00:00

  • No evidence of amyloidosis in type I diabetics treated with continuous subcutaneous insulin infusion.

    abstract::A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated wi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.1.88

    authors: Koivisto VA,Teppo AM,Maury CP,Taskinen MR

    更新日期:1983-01-01 00:00:00

  • Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process.

    abstract::Hyperglycemia-induced oxidative stress is detrimental for endothelial cells, contributing to the vascular complications of diabetes. The mitochondrial permeability transition pore (PTP) is an oxidative stress-sensitive channel involved in cell death; therefore, we have examined its potential role in endothelial cells ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.7.2179

    authors: Detaille D,Guigas B,Chauvin C,Batandier C,Fontaine E,Wiernsperger N,Leverve X

    更新日期:2005-07-01 00:00:00

  • Histologic differentiation of human fetal pancreatic explants transplanted into nude mice.

    abstract::The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the ti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.12.1180

    authors: Tuch BE,Ng AB,Jones A,Turtle JR

    更新日期:1984-12-01 00:00:00

  • Community screening for diabetes by blood glucose measurement. Results of a five-year experience.

    abstract::The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of th...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.12.1110

    authors: Genuth SM,Houser HB,Carter JR Jr,Merkatz I,Price JW,Schumacher OP,Wieland RG

    更新日期:1976-12-01 00:00:00

  • Risk of diabetes in siblings and other relatives of IDDM subjects.

    abstract::The risk of insulin-dependent diabetes mellitus (IDDM) was examined in siblings of an unselected population (n = 194) of newly diagnosed diabetic individuals less than 30 yr old. From 1 July 1984 to 30 June 1987, diabetic subjects (proband) identified within a geographically defined area of southern Wisconsin were stu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.7.831

    authors: Allen C,Palta M,D'Alessio DJ

    更新日期:1991-07-01 00:00:00

  • Calcium-calmodulin-dependent myosin phosphorylation by pancreatic islets.

    abstract::Pancreatic islets contain enzyme activity which catalyzes the phosphorylation by MgATP of cardiac, skeletal, or smooth muscle myosin light chains. The enzyme is activated by calcium (Ka = 10 microM) and calmodulin (Ka = 2 nM) and inhibited by trifluoperazine (Ki = 10 microM), a known inhibitor of calmodulin and of ins...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.31.6.566

    authors: MacDonald MJ,Kowluru A

    更新日期:1982-06-01 00:00:00

  • Triggering and amplifying pathways of regulation of insulin secretion by glucose.

    abstract::Glucose stimulates insulin secretion by generating triggering and amplifying signals in beta-cells. The triggering pathway is well characterized. It involves the following sequence of events: entry of glucose by facilitated diffusion, metabolism of glucose by oxidative glycolysis, rise in the ATP-to-ADP ratio, closure...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.49.11.1751

    authors: Henquin JC

    更新日期:2000-11-01 00:00:00

  • Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change.

    abstract::Because it is unknown whether 24-h energy expenditure (EE) responses to dietary extremes will identify phenotypes associated with weight regulation, the aim of this study was to determine whether such responses to fasting or overfeeding are associated with future weight change. The 24-h EE during energy balance, fasti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0382

    authors: Schlögl M,Piaggi P,Pannacciuli N,Bonfiglio SM,Krakoff J,Thearle MS

    更新日期:2015-11-01 00:00:00

  • Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients.

    abstract::To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjec...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.11.1318

    authors: Trovati M,Mularoni EM,Burzacca S,Ponziani MC,Massucco P,Mattiello L,Piretto V,Cavalot F,Anfossi G

    更新日期:1995-11-01 00:00:00

  • Short-term effect of insulin and 5(3-piridyl) tetrazole on serum triglycerides in insulin-dependent diabetic patients.

    abstract::A group of insulin-dependent diabetic patients was studied in order to determine the possible short-term regulatory effect of insulin and that of an antilipolytic drug on serum triglycerides. Subcutaneous crystalline insulin (one third of the usual morning dose of intermediate long-acting insulin, NPH) and an oral dos...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.26.7.615

    authors: Alvarez-Reynolds M,Dominguez JM

    更新日期:1977-07-01 00:00:00

  • Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis.

    abstract::Monocyte-to-macrophage differentiation is a critical event that accentuates atherosclerosis by promoting an inflammatory environment within the vessel wall. In this study, we investigated the molecular mechanisms responsible for monocyte-to-macrophage differentiation and, subsequently, the effect of metformin in regre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-1225

    authors: Vasamsetti SB,Karnewar S,Kanugula AK,Thatipalli AR,Kumar JM,Kotamraju S

    更新日期:2015-06-01 00:00:00

  • Accurate Measurement of Postprandial Glucose Turnover: Why Is It Difficult and How Can It Be Done (Relatively) Simply?

    abstract::Fasting hyperglycemia occurs when an excessive rate of endogenous glucose production (EGP) is not accompanied by an adequate compensatory increase in the rate of glucose disappearance (Rd). The situation following food ingestion is more complex as the amount of glucose that reaches the circulation for disposal is a fu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1166

    authors: Rizza RA,Toffolo G,Cobelli C

    更新日期:2016-05-01 00:00:00

  • Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes.

    abstract::Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.7.824

    authors: Beisswenger PJ,Makita Z,Curphey TJ,Moore LL,Jean S,Brinck-Johnsen T,Bucala R,Vlassara H

    更新日期:1995-07-01 00:00:00