Abstract:
:Cultured bovine retinal capillary pericytes (BRP) were used to investigate the effect of an aldose reductase inhibitor, tolrestat, and an inhibitor of advanced glycation end products (AGE) formation, aminoguanidine, on glucose toxicity. Glucose at high concentration reduced the replicative activity of pericytes in a dose-dependent manner. Tolrestat completely inhibited the production of sorbitol in cells exposed to a high concentration of glucose but failed to protect the cells from glucose toxicity. These results suggest that sorbitol accumulation in cells is probably not the major mechanism for glucose toxicity. In contrast, the addition of aminoguanidine at 10 mM concentration to the culture media protected pericytes from glucose toxicity. The degree of protected pericytes from glucose toxicity. The degree of protection was dose-dependent and evident at aminoguanidine concentration as low as 1 mM. The drug was only slightly toxic to BRP but induced morphological changes in pericytes with the loss of cellular processes and decreased cell spreading. This may suggest some action of aminoguanidine on the pericyte cytoskeleton. High concentration of glucose significantly increased the level of early glycation but not fluorescent AGE formation on BRP proteins. This was inhibited by the addition of aminoguanidine suggesting that glycation of cellular/membrane proteins and other mechanisms may play an important role in the toxic action of high glucose levels in cultured pericytes.
journal_name
Diabetesjournal_title
Diabetesauthors
Chibber R,Molinatti PA,Wong JS,Mirlees D,Kohner EMdoi
10.2337/diab.43.6.758subject
Has Abstractpub_date
1994-06-01 00:00:00pages
758-63issue
6eissn
0012-1797issn
1939-327Xjournal_volume
43pub_type
杂志文章相关文献
DIABETES文献大全abstract::Rats with chronic streptozotocin (SZ) diabetes develop dilatation of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving unmyelinated axons of the extrinsic innervation of the small bowel. Diabetic autonomic neuropathy involving the ileal mesenteric nerves is characterized by modest to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.6.532
更新日期:1983-06-01 00:00:00
abstract::Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.12.3342
更新日期:2004-12-01 00:00:00
abstract::The human leukocyte antigen (HLA) class II genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 has been identified as a marker strongly predisposing to insulin-dependent diabetes mellitus (IDDM) in Caucasian populations. Its frequency in control populations (1-3%) is still, however, 1 order of magnitude higher than the p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.5.527
更新日期:1995-05-01 00:00:00
abstract::Site differences in adipose tissue function may have implications for insulin-resistant conditions. In mature adipose tissue, subcutaneous adipocytes have higher leptin secretion, similar tumor necrosis factor (TNF)-alpha secretion, and lower catecholamine-stimulated lipolysis as compared with omental adipocytes. In t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.7.2029
更新日期:2002-07-01 00:00:00
abstract::The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2+/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1306
更新日期:2018-08-01 00:00:00
abstract::Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the reg...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.2.157
更新日期:2000-02-01 00:00:00
abstract::The aim of this study was to compare the effects of insulin and the insulinomimetic agent, englitazone, on functional end points and putative mediators of insulin action in 3T3-L1 adipocytes. Cells were incubated with englitazone for 48 h or with insulin for 10 or 30 min, or both, and 2-deoxy-D-[3H]glucose (2DG) uptak...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.2.179
更新日期:1998-02-01 00:00:00
abstract::Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogenous disorder characterized by defects in insulin action and secretion. This study was aimed at developing a rat model in which these pathogenic factors might be studied. Male Wistar rats were injected at 2 days of age with 45 or 30 mg/kg streptozocin (STZ) ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.2.226
更新日期:1990-02-01 00:00:00
abstract::To evaluate the role of splanchnic and peripheral tissues in the disposal of an oral glucose load, splanchnic exchange of glucose, lactate, pyruvate, glycerol and amino acids was determined in ten healthy subjects in the basal state and for three hours following the oral ingestion of 100 gm. of glucose. Following glu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.5.468
更新日期:1975-05-01 00:00:00
abstract::In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.41.2.s12
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVE:Macrophages play an important role in the pathogenesis of insulin resistance via the production of proinflammatory cytokines. Our goal is to decipher the molecular linkage between proinflammatory cytokine production and insulin resistance in macrophages. RESEARCH DESIGN AND METHODS:We determined cytokine pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0232
更新日期:2009-11-01 00:00:00
abstract::Clinical studies have shown a link between hyperuricemia (HU) and diabetes, while the exact effect of soluble serum urate on glucose metabolism remains elusive. This study aims to characterize the glucose metabolic phenotypes and investigate the underlying molecular mechanisms using a novel spontaneous HU mouse model ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0704
更新日期:2020-06-01 00:00:00
abstract::Transcription factor expression fluctuates during β-cell ontogeny, and disruptions in this pattern can affect the development or function of those cells. Here we uncovered that murine endocrine pancreatic progenitors express high levels of the homeodomain transcription factor Prox1, whereas both immature and mature β-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0713
更新日期:2016-03-01 00:00:00
abstract::Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and preve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0051
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVE:Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0873
更新日期:2009-12-01 00:00:00
abstract::The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.5.626
更新日期:1990-05-01 00:00:00
abstract::Islet transplantation for the treatment of autoimmune diabetes is more difficult because of the additional barrier presented by the autoimmunity. We tested the ability of hamster anti-rat CD154 to prevent recurrence of diabetes in renal subcapsular islet isografts in DR-BB (RT1uu) rats with established autoimmune diab...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.10.1666
更新日期:2000-10-01 00:00:00
abstract::We used hepatic balance and tracer ([3H]glucose) techniques to examine the impact of "breakfast" on hepatic glucose metabolism later in the same day. From 0-240 min, 2 groups of conscious dogs (n = 9 dogs/group) received a duodenal infusion of glucose (GLC) or saline (SAL), then were fasted from 240-360 min. Three dog...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1308
更新日期:2017-05-01 00:00:00
abstract::Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/diabetes.53.4.955
更新日期:2004-04-01 00:00:00
abstract::Pancreatic beta-cells are more sensitive to several toxins (e.g., streptozotocin, alloxan, cytokines) than the other three endocrine cell types in the islets of Langerhans. Cytokine-induced free radicals in beta-cells may be involved in beta-cell-specific destruction in type 1 diabetes. To investigate if this sensitiv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.12.2324
更新日期:1999-12-01 00:00:00
abstract::In vivo voltammetry was used to measure the synaptic release of rat striatal dopamine and serotonin after the administration of the amino acid L-tryptophan to streptozocin-induced diabetic rats. Dopamine and serotonin release from rat striatum was studied at a short-term or acute (3-day) interval and a long-term or ch...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.7.956
更新日期:1988-07-01 00:00:00
abstract::The molecular mechanism by which some, but not all, variants of encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice and induce IDDM has been an enigma for more than a decade. We report here that the binding site of the EMC viral capsid protein VP1 determines viral diabetogenicity. Recombi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.4.576
更新日期:1998-04-01 00:00:00
abstract::I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks ol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.10.969
更新日期:1978-10-01 00:00:00
abstract::Insulin receptor substrate (IRS)-1 protein expression is markedly reduced in many insulin-resistant states, although the mechanism for this downregulation is unclear. In this study, we have investigated the early events in the insulin pathway that trigger the degradation of IRS-1. Incubation of the adipocytes with ins...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.1.24
更新日期:2001-01-01 00:00:00
abstract::We recently showed that a peptide of the M(r) 60,000 heat shock protein molecule, designated peptide p277, is a target of T-cells in autoimmune diabetes in NOD mice. Indeed, the p277 peptide could be used as a therapeutic agent to arrest the autoimmune process even after it was far advanced. The present study was done...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.9.1132
更新日期:1995-09-01 00:00:00
abstract::Abnormalities of methyl-CpG binding protein 2 (Mecp2) cause neurological disorders with metabolic dysfunction; however, its role in adipose tissues remains unclear. Here, we report upregulated Mecp2 in white adipose tissues (WAT) of obese humans, as well as in obese mice and during in vitro adipogenesis. Normal chow-f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0502
更新日期:2020-01-01 00:00:00
abstract::Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL ar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0811
更新日期:2020-05-01 00:00:00
abstract::The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complic...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi18-0036
更新日期:2019-03-01 00:00:00
abstract::Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.9.1099
更新日期:1990-09-01 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