Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

Scalia, Rosario; Gong, Yulan; Berzins, Brett; Zhao, Li; Sharma, Kumar

doi:10.2337/db06-1198

Cited by 54 publications

(49 citation statements)

References 49 publications

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“…Hyperglycemia is recognized as a major factor in the pathogenesis of atherosclerosis in diabetes (Laakso 1999). High glucose had been reported to increase the permeability of ECs of umbilical vein (Dang et al 2005) or micro-vessels (Scalia et al 2007) in human. In the present study, high glucose incubation induced hyperpermeability in monolayer aortic ECs.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. b-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

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Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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“…associated with asthma (35). For example, high glucose acts directly on endothelial cells to increase endothelial permeability and increase leukocyte adhesion (57). Acute glucose challenge stimulates monocytes to increase expression of proinflammatory cytokines and chemokines (60) and stimulates release of reactive oxygen species (ROS) from leukocytes (46).…”

Section: Discussionmentioning

confidence: 99%

No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice

Shore¹,

Williams²,

Zhu³

2008

Journal of Applied Physiology

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Shore SA, Williams ES, Zhu M. No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice. J Appl Physiol 105: 1127-1133. First published August 14, 2008 doi:10.1152/japplphysiol.00117.2008.-We have previously reported that obese db/db mice exhibit innate airway hyperresponsiveness. These mice also have enhanced inflammatory responses to ozone, a common air pollutant that exacerbates asthma. Since db/db mice are diabetic as well as obese, the purpose of the present study was to determine whether metformin, an antihyperglycemic agent, alters the pulmonary phenotype of db/db mice. Lean wild-type (C57BL/6J) and obese db/db mice were treated by gavage with water or metformin (300 g/g) once a day for 2 wk. Twenty-four hours after the last treatment, in mice of both genotypes, we either measured airway responsiveness to methacholine by forced oscillation, or we exposed the mice to ozone (2 parts per million for 3 h) and examined the ensuing inflammatory response. Compared with water, treatment with metformin caused a significant decrease in fasting blood glucose in obese mice. Airway responsiveness was increased in db/db versus wild-type mice, but metformin did not affect responsiveness in either group. Four hours after exposure to ozone, there was a significant increase in bronchoalveolar lavage fluid neutrophils and chemokines in mice of both genotypes, but the magnitude of these changes was greater in db/db than wild-type mice. Metformin did not affect ozone-induced inflammation in mice of either genotype. The results indicate that hyperglycemia is unlikely to account for the pulmonary phenotype of obese mice. airway responsiveness; chemokine; inflammation; neutrophil; adiponectin OBESITY IS A RISK FACTOR for asthma. Multiple cross-sectional studies in large populations of adults and children of multiple ethnic backgrounds indicate that the prevalence of asthma is higher in obese and overweight individuals. In addition, several large prospective studies show that obesity antedates asthma (see recent reviews in Refs. 16, 61, and 63). Obese asthmatic patients who lose weight experience fewer asthma symptoms, increased airflow rates, reduced peak flow variability, and better asthma control (21,43,68). Obesity also appears to impact asthma control and the efficacy of certain asthma medications (13,36,51,55).Data from animal models also support a relationship between obesity and asthma. Obese mice exhibit airway hyperresponsiveness (AHR), a characteristic feature of asthma, even in the absence of any inciting exposure (31,32,34,41,54,66). This innate AHR is observed in ob/ob and db/db mice that are obese because of a genetic deficiency in either the satiety hormone, leptin, or its receptor; in Cpe fat mice that are obese because of a genetic deficiency in carboxypeptidase E (Cpe), an enzyme involved in processing neuropeptides involved in eating behaviors; and in mice with obesity induced by a high-fat diet (31,32,41,62,66). Obese mice have another feature con...

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“…36 Microvascular permeability to large molecules such as albumin is increased in diabetes, a process that is linked to hyperglycemia and ROS. 37 Several studies have shown impaired coronary flow reserve in diabetic individuals in the absence of coronary artery stenosis. 38 -41 In people with type 2 diabetes, coronary flow reserve is inversely related to hemoglobin A 1C and fasting plasma glucose levels, 39 which suggests that chronic hyperglycemia is a key factor.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Impaired Tissue Perfusion

et al. 2008

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Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

Cited by 54 publications

References 49 publications

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice

Impaired Tissue Perfusion

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