Abstract:
:The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increase in the PDGFbeta receptor that was inhibited by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway inhibitors. Exposure to 25 mmol/l D-glucose (HG) induced increased phosphorylation of protein kinase B (PKB) and extracellular-regulated kinase (ERK). All HG chemotaxis assays (with either 10 days' preincubation in HG or no preincubation) in a FCS or PDGF-BB gradient showed positive chemotaxis, whereas those in 5 mmol/l D-glucose did not. Assays were also run with concentrations ranging from 5 to 25 mmol/l D-glucose. Chemotaxis was induced at concentrations > or =9 mmol/l D-glucose. An anti-PDGFbeta receptor antibody inhibited glucose-potentiated VSMC chemotaxis, as did the inhibitors for the PI3K and MAPK pathways. This study has shown that small increases in D-glucose concentration, for a short period, increase VSMC expression of the PDGFbeta receptor and VSMC sensitivity to chemotactic factors in serum, leading to altered migratory behavior in vitro. It is probable that similar processes occur in vivo with glucose-enhanced chemotaxis of VSMCs, operating through PDGFbeta receptor-operated pathways, contributing to the accelerated formation of atheroma in diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Campbell M,Allen WE,Silversides JA,Trimble ERdoi
10.2337/diabetes.52.2.519subject
Has Abstractpub_date
2003-02-01 00:00:00pages
519-26issue
2eissn
0012-1797issn
1939-327Xjournal_volume
52pub_type
杂志文章相关文献
DIABETES文献大全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...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1342
更新日期:2018-08-01 00:00:00
abstract::Inactivation of the β-cell transcription factor NEUROD1 causes diabetes in mice and humans. In this study, we uncovered novel functions of NEUROD1 during murine islet cell development and during the differentiation of human embryonic stem cells (HESCs) into insulin-producing cells. In mice, we determined that Neurod1 ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0117
更新日期:2019-12-01 00:00:00
abstract::Diabetic patients have reduced antioxidant defenses and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. Epidemiological evidence has suggested that antioxidant dietary flavonoids may protect against heart disease, but a biological effect has yet to be demonstrated direct...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.1.176
更新日期:1999-01-01 00:00:00
abstract::To identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome, we performed a large-scale association study on 1,337 unrelated Japanese individuals, including 871 subjects with metabolic syndrome and 466 control subjects. Metabolic syndrome was diagnosed according to modi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1105
更新日期:2007-02-01 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::The selective impairment of glucose-induced insulin secretion in NIDDM can be attributed to defects in the glucose-signaling system. An alteration in the activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway, may play a role in the abnormal glucose-induced insulin secretion. In this study, we e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.9.1414
更新日期:1997-09-01 00:00:00
abstract::Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.1.s10
更新日期:1980-01-01 00:00:00
abstract::Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The object...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.3.508
更新日期:1997-03-01 00:00:00
abstract::The changes of the microvasculature of rat pancreas transplants during acute rejection were investigated and quantitatively analyzed. The vessels in pancreas transplants increased in caliber and decreased in density during acute rejection. These changes were marked in the exocrine pancreas, especially in central zones...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s111
更新日期:1989-01-01 00:00:00
abstract::Although many studies using rodent islets and insulinoma cell lines have been performed to determine the role of insulin in the regulation of islet function, the autocrine effect of insulin on insulin gene expression is still controversial, and no consensus has yet been achieved. Because very little is known about the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0532
更新日期:2006-10-01 00:00:00
abstract::Altered proteoglycan metabolism may play a role in the development of diabetic glomerulopathy. This study was conducted to examine the effects of glucose on the production and physical characteristics of proteoglycans generated by rat mesangial cells in culture. Rat mesangial cells were exposed to elevated glucose med...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.12.1815
更新日期:1993-12-01 00:00:00
abstract::Recent evidence demonstrates that hypothalamic insulin signaling is required for inhibition of endogenous glucose production. The downstream mechanisms that are responsible for the effects of hypothalamic insulin receptor activation on hepatic fuel flux remain to be determined. To establish whether downregulation of n...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2529
更新日期:2004-10-01 00:00:00
abstract::Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1737
更新日期:2002-06-01 00:00:00
abstract::Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is a promising strategy for combating obesity. Here, we find that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1901
更新日期:2014-09-01 00:00:00
abstract::The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.12.1040
更新日期:1980-12-01 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::We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.10.1217
更新日期:1989-10-01 00:00:00
abstract:OBJECTIVE:Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, re...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0724
更新日期:2008-07-01 00:00:00
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
更新日期:1984-12-01 00:00:00
abstract::O-linked N-acetylglucosamine transferase (OGT) catalyzes the attachment ofN-acetylglucosamine (GlcNAc) monosaccharides to the hydroxyl group of serine or threonine residues of intracellular proteins and may play an important role in the hexosamine pathway. Glucose-induced insulin resistance is mediated by increased ac...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.12.2407
更新日期:1999-12-01 00:00:00
abstract::Genetic susceptibility to type I diabetes is partly determined by genes located in the human leukocyte antigen (HLA) region on chromosome 6. It has been claimed that the transmission of HLA-encoded susceptibility is influenced by parental sex. Fathers are reported to transmit HLA-DR4 haplotypes more frequently to thei...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.12.1462
更新日期:1994-12-01 00:00:00
abstract::To test whether treatment with aminoguanidine, a drug known to prevent cross-linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.4.590
更新日期:1993-04-01 00:00:00
abstract:OBJECTIVE:Based on its role as an energy storage compartment and endocrine organ, white adipose tissue (WAT) fulfills a critical function in the maintenance of whole-body energy homeostasis. Indeed, WAT dysfunction is connected to obesity-related type 2 diabetes triggered at least partly by an inflammatory response in ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1537
更新日期:2010-08-01 00:00:00
abstract::Activation of the sympathetic nervous system (SNS) constitutes a putative mechanism of obesity-induced insulin resistance. Thus, we hypothesized that inhibiting the SNS by using renal denervation (RDN) will improve insulin sensitivity (SI) in a nonhypertensive obese canine model. SI was measured using euglycemic-hyper...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0698
更新日期:2016-11-01 00:00:00
abstract::We investigated the effects of obesity surgery-induced weight loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver. Furthermore, we determined the association of TCF7L2 splicing with the levels of plasma glucose and serum free fatty acids (FFAs) in three independent stud...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0239
更新日期:2012-11-01 00:00:00
abstract:OBJECTIVE:Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-ce...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1078
更新日期:2011-01-01 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::Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are incretins secreted by respective K and L enteroendocrine cells after eating and amplify glucose-stimulated insulin secretion (GSIS). This amplification has been termed the "incretin response." To determine the role(s) of K cells for the incretin response...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1188
更新日期:2015-04-01 00:00:00
abstract::Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality-iatrogenic hyperinsulinemia-principally drives ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/dbi19-0026
更新日期:2020-05-01 00:00:00
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
更新日期:2007-08-01 00:00:00