Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

Zhong, Mingkang; Shen, Weili; Tabuchi, Masaki; Nakamura, Kyoko; Chen, Yi‐Chen; Qiao, Congzhen; He, Jin; Yang, Jie; Zhang, Chuan; Kamenov, Zdravko; Higashino, Hideaki; Chen, Hong

doi:10.1155/2012/429020

Cited by 13 publications

(16 citation statements)

References 39 publications

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“…Hyperinsulinemia has been reported in OLETF rats in previous studies 7,8) . In the present analysis, metabolic correction with insulin notably reversed the enhanced endothelial function in the diabetic model rats, which may be due to the downregulation of endothelial nitric oxide synthase (eNOS)/heme oxygenase (HO)-1 9) .…”

Section: Ultrasound Assessments Of the Carotid Arterial Flow And Plaquementioning

confidence: 65%

“…In the present report, we demonstrated increased carotid arterial wall thickening and luminal narrowing in diabetic and obese rats. Typical metabolic syndrome leading to vessel dysfunction has been documented in OLETF rats 7,8) . We did not observe any vessel dysfunction in the present experiments; however, such dysfunction may worsen atherosclerotic changes.…”

Section: Ultrasound Assessments Of the Carotid Arterial Flow And Plaquementioning

confidence: 99%

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Carotid Artery Stenosis is Exacerbated in Spontaneously Obese Model Rats with Diabetes

Wajima

Nakagawa

Takamura

et al. 2014

JAT

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Aim: Population studies have shown obesity and diabetes to be risk factors for atherosclerosis. We assessed changes in the common carotid arteries in rat models of obesity and diabetes without hypertension. Methods: Twenty 30-week-old male spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF) and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the experiments. The animals were considered diabetic if the plasma glucose level peaked at ＞300 mg/dL and remained at ＞200 mg/dL for 120 minutes. Blood gas physiological parameters were continuously monitored under anesthesia, and the flow of the carotid artery was assessed with ultrasonography. All animals were sacrificed with an overdose of anesthesia at the end of the experiment. Sections of the middle portion of the internal carotid artery were cut and stained with hematoxylin and eosin to assess the overall morphology. Results: All OLETF rats were diabetic, and all LETO rats were non-diabetic. The physiological parameters did not differ significantly between the control and model rats, whereas the carotid artery wall thickness (19.3±3.2 vs. 6.1±4.5 μm) was significantly different between the two groups. The blood flow velocity in the common carotid artery determined using ultrasonography and color Doppler sonography was significantly increased during systole in the model rats compared with that observed in the control rats (203±20.3 vs. 55.3±21.4 cm/sec). Conclusions: The OLETF rats were obese, and diabetes worsened the degree of carotid artery stenosis. These results indicate the possibility of new therapies for carotid artery stenosis in obese and diabetic patients.

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Section: Ultrasound Assessments Of the Carotid Arterial Flow And Plaquementioning

confidence: 65%

Section: Ultrasound Assessments Of the Carotid Arterial Flow And Plaquementioning

confidence: 99%

Carotid Artery Stenosis is Exacerbated in Spontaneously Obese Model Rats with Diabetes

Wajima

Nakagawa

Takamura

et al. 2014

JAT

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“…Endothelial dysfunction affecting different blood vessels may not be consistent among different animal models of T2DM. For example, endothelium-dependent vasodilation in the aorta and carotid artery are preserved in lean diabetic Goto-Kakizaki rats, but impaired in obese diabetic Otsuka Long-Evans Tokushima Fatty rats (Zhong et al, 2012). Further studies using other systemic blood vessels (such as coronary and mesenteric arteries), and other animal models of T2DM are needed for comparison with the penile vascular bed in order to draw a more general conclusion.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats

Musicki¹,

Hannan

Lagoda³

et al. 2016

Andrology

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Men with type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) have greater risk of cardiovascular events than T2DM men without ED, suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2DM involves earlier redox imbalance and endothelial nitric oxidase synthase (eNOS) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2DM by high-fat diet for 2 weeks, followed by an injection with low-dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S-glutathionylation, oxidative stress (4-hydroxy-2-nonenal, 4-HNE), protein expression of NADPH oxidase subunit gp91phox, endothelium-dependent vasodilation in the carotid artery, and non-andrenergic, non-cholinergic (NANC) mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC mediated cavernosal relaxation were decreased (p<0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2DM rats. eNOS monomerization, protein expressions of 4-HNE and gp91phox, and protein S-glutathionylation, were increased (p<0.05) in the penis, but not in the carotid artery, of T2DM compared to nondiabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2DM in the penis, but not in the carotid artery. These molecular changes contribute to T2DM ED, while vascular function in the systemic vasculature remains preserved.

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“…Insulin resistance and hyperinsulinamia induce vessel wall thickening, and this thickness is found in OLETF rats at 30-week-old (9,12). Insulin resistance of vascular endothelial cells and subsequent vessel wall thickening cause dysregulation for blood vessel diameter and substance exchange (2,24). The dysfunction of endothelial vasodilation also impairs blood flow response in type 2 diabetes (15).…”

Section: Hemodynamic Responsementioning

confidence: 99%

“…Mild hyperbaric oxygen treatment could increase oxygen concentration and blood flow during the treatment (11), and reduction of hyperglycemia resulted from enhanced glucose metabolism in the skeletal muscle (4,17,20,23). Although 24) and Long-Evans Tokushima Otsuka (LETO, n = 22) rats were used as models of type 2 diabetes and healthy controls, respectively. The analysis was performed at 8 (OLETF n = 6, LETO n = 6), 20 (OLETF n = 6, LETO n = 5), 30 (OLETF n = 6, LETO n = 6), and 60-week-old (OLETF n = 6, LETO n = 5).…”

mentioning

confidence: 99%

Hemodynamic response during hyperbaric treatment on skeletal muscle in a type 2 diabetes rat model

et al. 2020

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Mild hyperbaric treatment prevents type 2 diabetes progression due to increased oxygen concentration and blood flow in skeletal muscle. However, it remains unknown whether this treatment is effective during all stages of type 2 diabetes. This study aimed to investigate the influences of hyperbaric treatment at 1.3 atmospheres absolute (ATA) on hemodynamic response in various stages of type 2 diabetes. Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as models of type 2 diabetes and healthy controls, respectively. Glucose levels were significantly higher in OLETF rats than in LETO rats at all ages. Glucose intolerance gradually increased with age in OLETF rats. Insulin levels in OLETF rats were significantly higher at 20-week-old, however, were significantly lower at 60-week-old than in LETO rats. Oxy-Hb, total Hb, and StO 2 in skeletal muscle were increased during hyperbaric treatment in both rats. The hemodynamic changes were significantly higher in OLETF rats than LETO rats, and those changes were also pronounced at 8-week-old compared with other age in OLETF rats. These results suggest that hyperbaric treatment at 1.3 ATA acts on pathophysiological factors and the efficacy could be found only in the early stage of type 2 diabetes.

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Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

Cited by 13 publications

References 39 publications

Carotid Artery Stenosis is Exacerbated in Spontaneously Obese Model Rats with Diabetes

Carotid Artery Stenosis is Exacerbated in Spontaneously Obese Model Rats with Diabetes

Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats

Hemodynamic response during hyperbaric treatment on skeletal muscle in a type 2 diabetes rat model

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