Abstract:
:The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functional receptor for the thiazolidinedione class of insulin-sensitizing drugs. This review examines the evidence that has implicated this transcription factor in the processes of adipogenesis and systemic insulin action. In addition, several models are discussed that may explain how a single protein can be involved in these related but distinct physiological actions. I also point out several important areas where our knowledge is incomplete and more research is needed. Finally, I discuss how advances in our understanding of nuclear receptor function, particularly the docking of cofactors in a ligand-dependent fashion, should lead to improved drugs that utilize the PPAR-gamma system for the treatment of insulin resistance.
journal_name
Diabetesjournal_title
Diabetesauthors
Spiegelman BMdoi
10.2337/diabetes.47.4.507subject
Has Abstractpub_date
1998-04-01 00:00:00pages
507-14issue
4eissn
0012-1797issn
1939-327Xjournal_volume
47pub_type
杂志文章,评审相关文献
DIABETES文献大全abstract::The current study investigated the fate of a [U-(13)C]palmitate tracer extracted by forearm muscle in type 2 diabetic and control subjects. We studied seven healthy lean male subjects and seven obese male subjects with type 2 diabetes using the forearm muscle balance technique with continuous intravenous infusion of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.784
更新日期:2002-03-01 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
abstract::Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, pol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.2.s74
更新日期:1991-12-01 00:00:00
abstract::We conducted a prospective study to describe the course of the pancreatic beta-cell function from the time of clinical diagnosis of insulin-dependent (type I) diabetes to determine whether DR type, presence of islet cell antibodies (ICA), presence of insulin antibodies (IA), age at onset, and sex could help in the pre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.7.920
更新日期:1988-07-01 00:00:00
abstract::Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data in humans are still sparse. We studied the frequency and activation state of blood NK cells at different stages of human type 1 diabetes, and whether genetic or phenotypic N...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0493
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (P...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0566
更新日期:2011-03-01 00:00:00
abstract::Children with permanent diabetes are usually assumed to have type 1 diabetes. It has recently been shown that there are genetic subgroups of diabetes that are often diagnosed during the neonatal period but may present later. A recent Italian study proposed that type 1 diabetes is rare before 6 months of age. We aimed ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0094
更新日期:2006-06-01 00:00:00
abstract::The effects of ethanol, acetaldehyde, and the two novel metabolites of ethanol 2,3-butanediol and 1,2-propanediol on basal and insulin-stimulated adipocyte lipogenesis and glucose oxidation in vitro were investigated. Whereas ethanol and acetaldehyde inhibited both processes at concentrations far greater than those fo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.7.912
更新日期:1988-07-01 00:00:00
abstract::Somatostatin-like immunoreactivity (SLI) concentrations were determined in human peripheral plasma using affinity chromatography followed by radioimmunoassay. In normal subjects, fasting SLI ranged from 2.9 to 22.0 pg/ml with a mean +/- SE value of 10.2 +/- 2.1 pg/ml. In totally pancreatectomized or gastrectomized pat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.6.471
更新日期:1981-06-01 00:00:00
abstract::We addressed the question of whether newly diagnosed type I (insulin-dependent) diabetes mellitus patients showed an increased number of DR (la+) T-lymphocytes compared with nondiabetic siblings and normal control subjects. Two-color flow cytometry measurements of peripheral-blood lymphocytes showed a slight but stati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.6.792
更新日期:1988-06-01 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::The soluble plant fiber psyllium significantly reduced fasting glucose and total cholesterol levels in the C57BL/KsJ db/db diabetic mouse relative to placebo-fed mice. Insulin levels were significantly higher in psyllium-fed than placebo-fed animals, indicating this fiber may delay the progression of diabetes in the a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.12.1528
更新日期:1989-12-01 00:00:00
abstract::Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; health...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.6.694
更新日期:1988-06-01 00:00:00
abstract::β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the rol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0022
更新日期:2013-09-01 00:00:00
abstract::Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of vari...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.44.3.330
更新日期:1995-03-01 00:00:00
abstract::Antibodies to islet cell proteins detected as 37,000 and 40,000 M(r), tryptic fragments (37- and 40-kDa antigens) are strongly associated with progression to IDDM. The 40-kDa antigen has recently been identified as the tyrosine phosphatase-like protein IA-2 (ICA512) whereas the 37-kDa antigen has been suggested to be ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.9.1187
更新日期:1996-09-01 00:00:00
abstract::We describe an automated method for the isolation of human pancreatic islets. The procedure meets the following requirements: 1) minimal traumatic action on the islets, 2) continuous digestion in which the islets that are progressively liberated can be saved from further enzymatic action, 3) minimal human intervention...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.4.413
更新日期:1988-04-01 00:00:00
abstract::ATP is known to be coreleased with insulin from pancreatic beta-cells. To monitor insulin secretion from single beta-cells, a single beta-cell was surrounded in culture by Fura 2-loaded calf pulmonary artery endothelium (CPAE) cells, which can detect the ATP. CPAE cells did not respond with an elevation in cytoplasmic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.10.1213
更新日期:1995-10-01 00:00:00
abstract::The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db15-0318
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:Visceral obesity and elevated plasma free fatty acids are predisposing factors for type 2 diabetes. Chronic exposure to these lipids is detrimental for pancreatic beta-cells, resulting in reduced insulin content, defective insulin secretion, and apoptosis. We investigated the involvement in this phenomenon of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1252
更新日期:2008-10-01 00:00:00
abstract::The hormonal responses to low-level exercise in pregnancy have been studied in 13 insulin-requiring diabetic patients and 42 control subjects. We found no significant changes in plasma glucose, epinephrine, glucagon, or FFA with this level of exercise in the study group and control subjects; but plasma norepinephrine ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.2.s78
更新日期:1985-06-01 00:00:00
abstract::The hyperglycemic patient remains persistently at risk for infectious complications. Whether ascribable to diabetes mellitus, to the administration of glucocorticoids, or to the infusion of hyperalimentation fluids, hyperglycemia may impair several mechanisms of humoral host defense, including such varied neutrophil f...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.39.3.271
更新日期:1990-03-01 00:00:00
abstract:OBJECTIVE:Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, b...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1433
更新日期:2010-07-01 00:00:00
abstract::Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control (CON) women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle, improving glucose uptake and metabolism in both healthy individuals and patients with type 2 diabetes. In...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0062
更新日期:2020-11-01 00:00:00
abstract::Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.11.3347
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE:Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity. RESEARCH DESIGN AND METHODS:Male C57BL/6J mice were fed a high-fat/high-sucrose diet...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1554
更新日期:2010-10-01 00:00:00
abstract::We have shown previously that palmitate treatment of C2C12 skeletal muscle myotubes causes inhibition of the protein kinase B (PKB) pathway and hence reduces insulin-stimulated glycogen synthesis through the elevation of intracellular ceramide levels. Ceramide is known to activate both atypical protein kinase C (aPKC)...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.10.2210
更新日期:2001-10-01 00:00:00
abstract::Regulated exocytosis forms the basis for many intercellular signaling processes, for example, in hormone secretion or neurotransmitter release. During regulated exocytosis, the membrane of a secretory vesicle fuses with the plasma membrane in a tightly controlled reaction that is most often triggered by calcium. Recen...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.2007.s3
更新日期:2002-02-01 00:00:00
abstract::Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0750
更新日期:2012-06-01 00:00:00