Abstract:
:Insulin resistance and type 2 diabetes are associated with elevated circulating levels of insulin, nonesterified fatty acids (NEFAs), and lipoprotein remnants. Extracellular matrix proteoglycan (PG) alterations are also common in macro- and microvascular complications of type 2 diabetes. In liver, extracellular heparan sulfate (HS) PGs contribute to the uptake of triglyceride-rich lipoprotein remnants. We found that HepG2 cells cultured with 10 or 50 nmol/l insulin or 300 micromol/l albumin-bound linoleic acid changed their PG secretion. The glycosaminoglycans (GAGs) of the secreted PGs from insulin-treated HepG2 cells were enriched in chondroitin sulfate (CS) PGs. In contrast, cells exposed to linoleic acid secreted PGs with decreased content of CS. Insulin caused a moderate increase in mRNA for versican (secreted CS PG), whereas linoleic acid markedly decreased mRNA for versican in HepG2 cells, as did the peroxisomal proliferator-activated receptor-alpha agonist bezafibrate. The effects of insulin or linoleic acid on syndecan 1, a cell surface HS PG, were similar to those on versican, but less pronounced. The livers of obese Zucker fa/fa rats, which are insulin-resistant and have high levels of insulin, NEFAs, and triglyceride-rich remnants, showed increased expression of CS PGs when compared with lean littermates. These changes in PG composition decreased the affinity of remnant beta-VLDL particles to PGs isolated from insulin-treated HepG2 cells and obese rat livers. The results indicated that insulin and NEFAs modulate the expression of PGs in hepatic cells. We speculate that in vivo this exchange of CS for HS may reduce the clearance of remnant beta-VLDLs and contribute to the dyslipidemia of insulin resistance.
journal_name
Diabetesjournal_title
Diabetesauthors
Olsson U,Egnell AC,Lee MR,Lundén GO,Lorentzon M,Salmivirta M,Bondjers G,Camejo Gdoi
10.2337/diabetes.50.9.2126subject
Has Abstractpub_date
2001-09-01 00:00:00pages
2126-32issue
9eissn
0012-1797issn
1939-327Xjournal_volume
50pub_type
杂志文章相关文献
DIABETES文献大全abstract::Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. We examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.11.2720
更新日期:2003-11-01 00:00:00
abstract::Development of beta-cell lines for cell therapy of diabetes is hindered by functional deviations of the replicating cells from the normal beta-cell phenotype. In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.9.1419
更新日期:1998-09-01 00:00:00
abstract:OBJECTIVE:Recently, several drugs have been shown to exert beneficial effects for metabolic syndrome through mild regulation of mitochondrial function. Hence, we explored a strategy of targeting mitochondrial function to improve glucose and lipid metabolism. RESEARCH DESIGN AND METHODS:Mitochondrial membrane potential...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0223
更新日期:2010-01-01 00:00:00
abstract::A 5-day culture of adult rat islets with human recombinant IL-1 beta (3 U/ml) resulted in the death of most alpha-cells and 50% of beta-cells. The IL-1--exposed islet tissue contained--in addition to poorly granulated beta-cells--patches of outgrowing monolayers and dispersed activated macrophages. In purified alpha- ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.1.56
更新日期:1993-01-01 00:00:00
abstract::Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli wer...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.130
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic beta-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in beta-cells by an RNA interference t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0970
更新日期:2009-03-01 00:00:00
abstract::In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the u...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.5.667
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVE:Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk. RESEARCH DESIGN AND METHODS:Eight subjects with risk-conferring TCF7L2 genotypes (TT o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1169
更新日期:2010-02-01 00:00:00
abstract::Insulin signaling in vascular endothelial cells (ECs) is critical to maintain endothelial function but also to mediate insulin action on peripheral glucose disposal. However, gene knockout studies have reached disparate conclusions. Thus, insulin receptor inactivation in ECs does not impair insulin action, whereas ina...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1296
更新日期:2013-05-01 00:00:00
abstract:OBJECTIVE:Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo are less well characterized....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0706
更新日期:2008-02-01 00:00:00
abstract::Wilson and coworkers (Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, Porcelli S, Schatz DA, Atkinson MA, Balk SP, Strominger JL, Hafler DA: Extreme Th1 bias of invariant V alpha24J alpha Q T-cells in type 1 diabetes. Nature 391:177-181, 1998) have recently reported raised serum levels of interleukin-4 (I...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.11.2166
更新日期:1999-11-01 00:00:00
abstract::Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. The recent escalation of obesity in affluent cou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-1273
更新日期:2013-07-01 00:00:00
abstract::Fasting plasma glucose concentrations (FPG) predict development of type 2 diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or as a step increase is not known. We measured plasma glucose and insulin levels during oral glucose testing in 35- to 64-year-old men and nonpregnant women from a p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.1.160
更新日期:2004-01-01 00:00:00
abstract::Zucker (fa/fa) rats with defective leptin receptors are obese, hyperphagic, and hyperinsulinemic. For testing whether chronic activation of the central melanocortin pathway can bypass the defective leptin signaling and normalize altered energy homeostasis in these rats, recombinant adeno-associated virus encoding pro-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.8.1951
更新日期:2003-08-01 00:00:00
abstract:OBJECTIVE:Paracrine signaling via gamma-aminobutyric acid (GABA) and GABA(A) receptors (GABA(A)Rs) has been documented in rodent islets. Here we have studied the importance of GABAergic signaling in human pancreatic islets. RESEARCH DESIGN AND METHODS:Expression of GABA(A)Rs in islet cells was investigated by quantita...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0797
更新日期:2010-07-01 00:00:00
abstract::Insulin levels in humans were measured by a new assay, the isotope dilution assay (IDA), based on stable isotope dilution mass spectrometry. A known amount of a deuterated analog of insulin was used as an internal standard and added to the serum samples before sample processing. After isolation by immunoaffinity chrom...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.1.44
更新日期:1997-01-01 00:00:00
abstract::We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1588
更新日期:2017-07-01 00:00:00
abstract::Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0578
更新日期:2017-11-01 00:00:00
abstract::It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provides first insight int...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.2.233
更新日期:2000-02-01 00:00:00
abstract::Recently, a new stage in glucose tolerance, impaired fasting glucose (IFG) (fasting plasma glucose level of 6.1-6.9 mmol/l), was introduced in addition to impaired glucose tolerance (IGT) (2-h glucose level of 7.8-11.0 mmol/l). It is not clear whether IFG and IGT differ with respect to insulin secretion or sensitivity...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.6.975
更新日期:2000-06-01 00:00:00
abstract::Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0079
更新日期:2019-09-01 00:00:00
abstract::Body weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1694
更新日期:2014-12-01 00:00:00
abstract::Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.5.398
更新日期:1983-05-01 00:00:00
abstract::Although obesity rates are rapidly rising, caloric restriction remains one of the few safe therapies. Here we tested the hypothesis that obesity-associated disorders are caused by increased adipose tissue as opposed to excess dietary lipids. Fat mass (FM) of lean C57B6 mice fed a high-fat diet (HFD; FMC mice) was "cla...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1621
更新日期:2012-11-01 00:00:00
abstract::Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial funct...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0117
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose tr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0120
更新日期:2011-07-01 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::Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.228
更新日期:1999-01-01 00:00:00
abstract::Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.7.640
更新日期:1979-07-01 00:00:00
abstract::RT6 is a glycosyl-phosphatidylinositol-linked surface molecule present on most mature rat T-cells. RT6+ T-cells can prevent the expression of autoimmune diabetes in the BB rat, but the mechanism is unknown. Because cross-linking of other glycosyl-phosphatidylinositol-linked T-cell proteins is known to activate T-cells...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.10.1419
更新日期:1996-10-01 00:00:00