In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

Huang, Hsiao Ning; Lu, Pei Jung; Lo, Wan Chen; Lin, Chia Hui; Hsiao, Michael; Tseng, Ching Jiunn

doi:10.1161/01.cir.0000145116.75657.2d

Cited by 41 publications

(50 citation statements)

References 42 publications

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“…These observations suggest that an impaired response to hyperthermia in activating Akt in a PI 3-kinase-dependent manner underlies the mechanism for depressed HSP72 expression in the STZ-induced diabetic heart. Regarding the mechanisms involved, it is noteworthy that insulin reportedly activates Akt in a PI 3-kinase-dependent manner in several cell types, including cardiomyocytes (12,13). In the present study, insulin treatment restored hyperthermia-induced HSP72 expression in the STZ-induced diabetic heart.…”

Section: Discussionsupporting

confidence: 54%

“…However, little is known about the involvement of Akt in hyperthermia-induced HSP72 expression in the heart. Because insulin activates Akt in a PI 3-kinase-dependent manner (12,13), we hypothesized that 1) whole-body hyperthermia could cause PI 3-kinasedependent activation of Akt in the normal heart, resulting in HSP72 overexpression in association with protection against ischemia-reperfusion injury, and 2) insulin-deficient STZ-induced diabetic rats have impaired PI 3-kinasedependent activation of Akt, which results in the loss of hyperthermia-induced myocardial HSP72 expression and cardioprotection.…”

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confidence: 99%

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Phosphatidylinositol 3-Kinase–Dependent Activation of Akt, an Essential Signal for Hyperthermia-Induced Heat-Shock Protein 72, Is Attenuated in Streptozotocin-Induced Diabetic Heart

et al. 2006

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We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. STZ-induced male diabetic rats were treated with insulin (STZ-insulin group, n ‫؍‬ 26) or vehicle (STZ-vehicle group, n ‫؍‬ 61) for 3 weeks. Whole-body hyperthermia (43°C for 20 min) was applied, and the heart was isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZvehicle heart. Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia-treated STZ-vehicle heart showed poor left ventricular functional recovery during reperfusion after no-flow global ischemia compared with hyperthermiatreated control heart. Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. In cultured neonatal rat cardiomyocytes, hyperthermiainduced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency. Diabetes 55: 1307-1315, 2006 S tudies from our laboratory and those of other investigators have shown that heat-shock protein 72 (HSP72), induced by hyperthermia, protects the heart against ischemia-reperfusion injury (1-3). Streptozotocin (STZ)-induced diabetic rats have been widely used as a model of insulin-deficient diabetes and are known to exhibit various cardiac abnormalities (4). However, the effects of STZ-induced diabetes on HSP72 expression in the heart remain inconclusive. Joyeux et al. (5) reported that, although hyperthermia induced comparable expression levels of HSP72 in normal and diabetic hearts, the size of the infarction induced by coronary artery occlusion followed by reperfusion was larger in the diabetic than in the normal heart. Based on these observations, Joyeux et al. (5) concluded that the myocardial protective effect of hyperthermia did not extend to STZ-induced diabetic rats and seemed to be unrelated to the HSP72 level. Recently, however, Qi et al. (6) reported that preconditioning with a -opioid receptor agonist, U50,488H, increased cardiac HSP72 expression and reduced the infarct size induced by coronary artery occlusion in the normal heart 24 h after preconditioning but not in the STZ-induced diabetic rat heart. They concluded that lack of a U50,488H cardioprotective effect could, at least in part, be due to impaired synthesis of HSP72 in the STZ-induced diabetic heart (6).Activation of Akt prom...

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Section: Discussionsupporting

confidence: 54%

mentioning

confidence: 99%

Phosphatidylinositol 3-Kinase–Dependent Activation of Akt, an Essential Signal for Hyperthermia-Induced Heat-Shock Protein 72, Is Attenuated in Streptozotocin-Induced Diabetic Heart

et al. 2006

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“…Activation of PI3K/Akt pathway is a key step for diverse biological effects, including cell proliferation, growth, and survival [24,25]. Therefore, cellular activities brought about by the Rg1-activated PI3K/Akt pathway via the specific binding with the GR warrant further investigations.…”

Section: Discussionmentioning

confidence: 99%

Signaling pathway of ginsenoside‐Rg1 leading to nitric oxide production in endothelial cells

et al. 2006

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We here provide definitive evidence that ginsenosideRg1, the pharmacologically active component of ginseng, is a functional ligand of the glucocorticoid receptor (GR) as determined by fluorescence polarization assay. Rg1 increased the phosphorylation of GR, phosphatidylinositol-3 kinase (PI3K), Akt/PKB and endothelial nitric oxide synthase (eNOS) leading to increase nitric oxide (NO) production in human umbilical vein endothelial cell. Rg1-induced eNOS phosphorylation and NO production were significantly reduced by RU486, LY294,002, or SH-6. Also, knockdown of GR completely eliminated the Rg1-induced NO production. This study revealed that Rg1 can indeed serve as an agonist ligand for GR and the activated GR can induce rapid NO production from eNOS via the non-transcriptional PI3K/Akt pathway.

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“…4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity. 4,5 Furthermore, sympathectomy can prevent the development of fructose-induced hypertension in rats. 6 Recent studies suggest that fructose consumption increases superoxide generation and attenuates baroreflex response.…”

mentioning

confidence: 99%

“…2,3 However, insulin infusion was found to stimulate local vasodilation by enhancing the action of nitric oxide (NO). 4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity. 4,5 Furthermore, sympathectomy can prevent the development of fructose-induced hypertension in rats.…”

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confidence: 99%

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

et al. 2014

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535I n humans, the intake of sugar-sweetened beverages is correlated with the prevalence of type 2 diabetes mellitus and obesity.1 High fructose intake is used as a well-established animal model for insulin resistance.2 Some studies have shown that chronic fructose intake in normal rats induces hypertension in association with insulin resistance.2,3 However, insulin infusion was found to stimulate local vasodilation by enhancing the action of nitric oxide (NO). 4 The effect of insulin on the baroreceptor reflex in nucleus tractus solitarii (NTS) is probably mediated by a change in sympathetic nervous activity. 4,5 Furthermore, sympathectomy can prevent the development of fructose-induced hypertension in rats. 6 Recent studies suggest that fructose consumption increases superoxide generation and attenuates baroreflex response. 7,8 Interestingly, inhibition of superoxide generation in NTS can reduce blood pressure (BP) in stroke-prone hypertensive rats. 9 The NTS is located in the dorsal medulla of the brain stem, which is the primary integrating center for cardiovascular regulation and other autonomic functions of the central nervous system. Furthermore, NO has important modulatory functions in the NTS, including the modulation of arterial BP and sympathetic nerve activity. 10 In previous experiments, we demonstrated that insulin microinjected into the NTS induces a depressor effect and initiates an interaction between insulin and phosphatidylinositol 3-kinase Abstract-Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructoseinduced phosphorylation of insulin receptor substrate 1 (IRS1 S307) and reversed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production o...

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In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

Cited by 41 publications

References 42 publications

Phosphatidylinositol 3-Kinase–Dependent Activation of Akt, an Essential Signal for Hyperthermia-Induced Heat-Shock Protein 72, Is Attenuated in Streptozotocin-Induced Diabetic Heart

Phosphatidylinositol 3-Kinase–Dependent Activation of Akt, an Essential Signal for Hyperthermia-Induced Heat-Shock Protein 72, Is Attenuated in Streptozotocin-Induced Diabetic Heart

Signaling pathway of ginsenoside‐Rg1 leading to nitric oxide production in endothelial cells

Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling

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