Zucker Diabetic Fatty rats exhibit hypercoagulability and accelerated thrombus formation in the Arterio-Venous shunt model of thrombosis

Shang, Jin; Zhu, Caihong; Wang, Min; Li, Qiu; Feng, Wen; Wu, Yangsong; Wu, Wei; Graziano, Michael P.; Chintala, Madhu

doi:10.1016/j.thromres.2014.04.008

Cited by 20 publications

(20 citation statements)

References 42 publications

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“…In one study, Zucker diabetic rats fed high-fat diets demonstrated enhanced thrombin-generating potential compared with lean controls, regardless of glycemic control. 40 In a second study, Wistar weanling rats maintained on high-fat diets had increased ETP compared with low-fat diet controls. 41 The assay methods, trigger reagents, blood collection site, centrifugation, and storage conditions all varied between these studies, demonstrating the current lack of standardization for TGA in animal studies.…”

Section: Discussionmentioning

confidence: 94%

“…Recent studies have included TGA to characterize procoagulant excess in rat models of metabolic disease. In one study, Zucker diabetic rats fed high‐fat diets demonstrated enhanced thrombin‐generating potential compared with lean controls, regardless of glycemic control . In a second study, Wistar weanling rats maintained on high‐fat diets had increased ETP compared with low‐fat diet controls .…”

Section: Discussionmentioning

confidence: 99%

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Preanalytic processing of rat plasma influences thrombin generation and fibrinolysis assays

Brooks

Stablein

Johnson

et al. 2017

Veterinary Clinical Pathol

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Preanalytic processing of rat plasma influences thrombin generation and fibrinolysis assays

Brooks

Stablein

Johnson

et al. 2017

Veterinary Clinical Pathol

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“…Female Zucker diabetic fatty [fZDF (fa/fa)] rats and age-and gender-matched genetic control Zucker lean (ZL) rats were purchased at 6 weeks of age from the Charles River Laboratories (Wilmington, MA). The fZDF rats were fed a high-fat, high-carbohydrate diet (Research Diets D10111701, 48% kcal from fat and 34% kcal from carbohydrate, Research Diets, New Brunswick, NJ) for 3-4 weeks to induce hyperglycemia (23). The ZL rats were fed a chow diet (Research Diets D7012).…”

Section: Chronic Prevention Treatment In Female Zucker Diabetic Fattymentioning

confidence: 99%

GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy

Satapati

Qian

et al. 2017

Journal of Lipid Research

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GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in / mice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy. Compared with a GPR40 selective agonist, the dual agonist improved insulin sensitivity in mice measured by hyperinsulinemic-euglycemic clamp, preserved islet morphology, and increased expression of several key lipolytic genes in adipose tissue of Zucker diabetic fatty rats. Novel insights into the mechanism of action for GPR120 were obtained. Selective GPR120 activation suppressed lipolysis in primary white adipocytes, although this effect was attenuated in adipocytes from obese rats and obese rhesus, and sensitized the antilipolytic effect of insulin in rat and rhesus primary adipocytes. In conclusion, GPR120 agonism enhances insulin action in adipose tissue and yields a synergistic efficacy when combined with GPR40 agonism.

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“…This tends not to be exceptionally large (on the order of 25-30 mmHg), but it is consistent. Developing in parallel with all of these pathologies is a steady elevation in the pro-oxidant (Henriksen et al 2011), pro-inflammatory (Naka et al 2004) and pro-thrombotic (Shang et al 2014) state of the OZR, and this can readily be identified through standard assays for the appropriate plasma and vascular biomarkers of reactive oxygen species, inflammatory cytokines and adipokines, and intermediates in the coagulation cascade. Taken together, it is evident that the OZR represents an excellent model for the metabolic syndrome in human subjects and not only manifests the appropriate pathologies, but also to an appropriate level of severity.…”

Section: The Obese Zucker Rat (Ozr) Model Of the Metabolic Syndromementioning

confidence: 99%

“…) and pro‐thrombotic (Shang et al . ) state of the OZR, and this can readily be identified through standard assays for the appropriate plasma and vascular biomarkers of reactive oxygen species, inflammatory cytokines and adipokines, and intermediates in the coagulation cascade. Taken together, it is evident that the OZR represents an excellent model for the metabolic syndrome in human subjects and not only manifests the appropriate pathologies, but also to an appropriate level of severity.…”

Section: Introductionmentioning

confidence: 99%

Microvascular perfusion heterogeneity contributes to peripheral vascular disease in metabolic syndrome

Frisbee

Goodwill

Frisbee

et al. 2014

The Journal of Physiology

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A major challenge facing public health is the increased incidence and prevalence of the metabolic syndrome, a clinical condition characterized by excess adiposity, impaired glycaemic control, dyslipidaemia and moderate hypertension. The greatest concern for this syndrome is the profound increase in risk for development of peripheral vascular disease (PVD) in afflicted persons. However, ongoing studies suggest that reductions in bulk blood flow to skeletal muscle may not be the primary contributor to the premature muscle fatigue that is a hallmark of PVD. Compelling evidence has been provided suggesting that an increasingly spatially heterogeneous and temporally stable distribution of blood flow at successive arteriolar bifurcations in metabolic syndrome creates an environment where a large number of the pre-capillary arterioles have low perfusion, low haematocrit, and are increasingly confined to this state, with limited ability to adapt perfusion in response to a challenged environment. Single pharmacological interventions are unable to significantly restore function owing to a divergence in their spatial effectiveness, although combined therapeutic approaches to correct adrenergic dysfunction, elevated oxidant stress and increased thromboxane A 2 improve perfusion-based outcomes. Integrated, multi-target therapeutic interventions designed to restore healthy network function and flexibility may provide for superior outcomes in subjects with metabolic syndrome-associated PVD.

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Zucker Diabetic Fatty rats exhibit hypercoagulability and accelerated thrombus formation in the Arterio-Venous shunt model of thrombosis

Cited by 20 publications

References 42 publications

Preanalytic processing of rat plasma influences thrombin generation and fibrinolysis assays

Preanalytic processing of rat plasma influences thrombin generation and fibrinolysis assays

GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy

Microvascular perfusion heterogeneity contributes to peripheral vascular disease in metabolic syndrome

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