Altered insulin-mediated and insulin-like growth factor-1-mediated vasorelaxation in aortas of obese Zucker rats

Yang, Ai‐Lun; Chao, Jung-I; Lee, Shin-Da

doi:10.1038/sj.ijo.0803364

Cited by 19 publications

(11 citation statements)

References 30 publications

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“…Moreover, insulin and IGF-1 have been found to be involved in the development of many cardiovascular diseases, such as hypertension and diabetes mellitus (Goke & Fehmann, 1996;Vecchione et al 2001;McCallum et al 2005). Our laboratory had also reported that decreased insulin-induced vasorelaxation appeared to be countered by the increased IGF-1-induced vasorelaxation in obese rats (Yang et al 2007). In the present study, significant impairment of insulin-and IGF-1-induced vasorelaxation was found in spontaneously hypertensive rats.…”

Section: Discussionsupporting

confidence: 60%

“…However, the differential actions of insulin and IGF-1 contributing to cardiovascular diseases are not totally understood. Altered vascular function mediated by insulin and IGF-1 has been reported in some cardiovascular diseases, such as hypertension and obesity (Vecchione et al 2001;McCallum et al 2005;Yang et al 2007). Specifically, one study indicated that the attenuation of phenylephrineinduced constriction by insulin/IGF-1 was dysfunctional in hypertensive rats (McCallum et al 2005).…”

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confidence: 99%

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Aerobic exercise acutely improves insulin‐ and insulin‐like growth factor‐1‐mediated vasorelaxation in hypertensive rats

Yang¹,

Yeh

et al. 2010

Experimental Physiology

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Limited information is available concerning the effects of aerobic exercise on vasorelaxation in hypertension. The aim of this study was to investigate the effects of a single bout of aerobic exercise on insulin-and insulin-like growth factor-1 (IGF-1)-induced vasorelaxation in hypertensive rats. Four-month-old spontaneously hypertensive rats were randomly divided into a sedentary group (SHR) and an exercise group (SHR+Ex) subjected to a single bout of aerobic exercise conducted by treadmill running at 21 m min −1 for 1 h. Age-matched WistarKyoto rats were used as a normotensive control group (WKY). Insulin-and IGF-1-induced vasorelaxant responses in the three groups were evaluated by using isolated aortic rings, with or without endothelial denudation, in organ baths. Possible roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) involved in the NO-dependent vasorelaxation were examined by adding selective inhibitors. The role of superoxide was also clarified by adding superoxide dismutase (SOD). In addition, the endothelium-independent vascular responses to sodium nitroprusside (SNP), a NO donor, were examined. The insulin-and IGF-1-induced vasorelaxation was significantly (P < 0.05) decreased in the SHR group compared with the WKY group. This decreased response in SHR was improved by exercise. These vasorelaxant responses among the three groups became similar after endothelial denudation and pretreatment with the PI3K inhibitor, NOS inhibitor or SOD. Also, no difference among groups was found in the SNP-induced vasorelaxation. We concluded that a single bout of aerobic exercise acutely improves insulin-and IGF-1-mediated vasorelaxation in an endothelium-dependent manner in hypertensive rats.

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Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 99%

Aerobic exercise acutely improves insulin‐ and insulin‐like growth factor‐1‐mediated vasorelaxation in hypertensive rats

Yang¹,

Yeh

et al. 2010

Experimental Physiology

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“…Based on our data that IGF1R expression is upregulated in the vasculature of diabetic animals, we propose that hybrid receptor formation may contribute to vascular insulin resistance and pathology in vivo . This is supported by data showing that insulin-induced vasorelaxation in aortas of obese rats is significantly decreased, whereas IGF-1-induced vasorelaxation is profoundly increased, compared with that in lean rats 32. Similarly, IGF1R is upregulated and IGF-1-mediated aortic relaxation is increased after induction of diabetes by streptozotocin in rats 33…”

Section: Discussionmentioning

confidence: 64%

Insulin-Like Growth Factor-1 Receptor Expression Masks the Antiinflammatory and Glucose Uptake Capacity of Insulin in Vascular Smooth Muscle Cells

Engberding

Martín

Martín-Garrido

et al. 2009

ATVB

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Objective Insulin resistance of vascular smooth muscle cells (VSMCs) has been linked to accelerated atherosclerosis in diabetes; however, the effects of insulin on VSMCs remain controversial. Most VSMC insulin receptors are sequestered into insulin-insensitive hybrids with insulin-like growth factor-1 receptors (IGF1R). Thus we hypothesized that regulation of IGF1R expression may impact cellular insulin sensitivity. Methods and Results IGF1R expression was increased in aortas from diabetic mice. IGF1R overexpression in VSMCs impaired insulin-induced Akt phosphorylation. Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin-induced phosphorylation of its receptor, Akt, Erk1/2 and further augmented insulin-induced glucose uptake. IGF1R downregulation uncovered an insulin-induced reduction in activation of NF-κB and inhibition of MCP-1 upregulation in response to TNF-α. Conclusions Downregulation of IGF1R increases the fraction of insulin receptors organized in holoreceptors, which leads to enhanced insulin signaling and unmasks potential anti-inflammatory properties of insulin in VSMCs. Therefore, IGF1R, which is susceptible to feedback regulation by its own ligand, may represent a novel target for interventions designed to treat insulin resistance in the vasculature.

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“…59 IGF-1 can stimulate NO production from endothelial and vascular smooth-muscle cells, indicating a vascular protective function. 60 IGF-1 also has antiapoptotic and neuroprotective effects. 61 In addition, serum IGF-1 levels are correlated significantly with muscle strength and physical performance.…”

Section: Growth Hormonementioning

confidence: 99%

Nutritional and Botanical Approaches to Antiaging

Meletis¹,

Zabriskie²

2006

Alternative and Complementary Therapies

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A s the human population ages and increases in longevity, study of biological aging is emerging. According to the Centers for Disease Control and Prevention, for 2003, an estimated 35.9 million Americans were over the age of 65 and more than 25 percent of this population was in fair-to-poor health. 1 The mechanism of cellular aging is elusive and many theories have been proposed to explain the decrease in physiologic function that occurs with aging. As a result of increased risks of disease and mortality, decreases in quality of life, and rising health care costs, aging and longevity research is necessary to address problems related to aging. A wide range of nutrients and interventions have been shown to decrease cellular aging and age-related disease. Theories of Aging There are several theories of cellular aging. These theories are not mutually exclusive, and many complement each other. Aging was initially believed to be a result of genetically programmed cell death. Subsequently, it was proposed that aging might be a result of accumulation of cellular damage and mutation. Given that evidence has surfaced suggesting that aging may be a result of cellular damage, this implies that interventions to influence aging are possible. Oxidative Stress and Free Radicals Damage caused by free radicals is the most popular and universal theory of cellular aging. These highly reactive molecules are formed in many biochemical reactions as well as being introduced via exogenous exposures. Free radicals react with molecules causing damage and mutations, and have been implicated in many disease processes. 2 Studies indicate that an increase in the accumulation of oxidative damage increases functional deficits during aging, and treatments that decrease oxidative damage have been shown to delay age-related loss of function. 3 Other evidence suggests that increases in oxidative stress cause increases in inflammatory mediators, leading to age-related inflammatory diseases, such as arthritis, atherosclerosis, osteoporosis, and dementia. 4 Mitochondrial Damage Mitochondria produce most of the energy used by the body in the form of adenosine triphosphate (ATP). Oxidative phosphorylation provides the majority of ATP production via the electron transport chain. Aging has been shown to decrease the efficiency of mitochondrial oxidative phosphorylation. Specifically, aging decreases cellular energy production, impairs substrate oxidation, and increases the production of free radicals. 5 Loss of muscle mass and function seen with aging is associated with mitochondrial damage in muscle cells. 6 Studies indicate that aging is associated with a decrease in number and increase in size of mitochondria, making them less efficient with age. 7 Small amounts of reactive oxygen species (ROS) are formed via energy production that regulates some cellular functions, and that can act as a second messenger for transcription factors. 8 Cells have several antioxidant enzymes to prevent excess ROS from causing damage. Enzymes required for oxidative phosphory...

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Altered insulin-mediated and insulin-like growth factor-1-mediated vasorelaxation in aortas of obese Zucker rats

Cited by 19 publications

References 30 publications

Aerobic exercise acutely improves insulin‐ and insulin‐like growth factor‐1‐mediated vasorelaxation in hypertensive rats

Aerobic exercise acutely improves insulin‐ and insulin‐like growth factor‐1‐mediated vasorelaxation in hypertensive rats

Insulin-Like Growth Factor-1 Receptor Expression Masks the Antiinflammatory and Glucose Uptake Capacity of Insulin in Vascular Smooth Muscle Cells

Nutritional and Botanical Approaches to Antiaging

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