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ABSTRACT: Aim: Diabetes mellitus associated hyperglycemia and oxidative stress has been shown to have detrimental effects on the brain and may lead to impairment of cognitive functions. Resveratrol (Rsv), a polyphenolic antioxidant, has been shown to have moderate hypoglycemic and prominent hypolipidemic effects in diabetic rats. In the present study, we examined if Rsv improves the diabetic encephalopathy and explored its possible underlying mechanisms. Methods: Male SD rats were treated with streptozotocin (STZ, 65 mg/kg), and the diabetic rats were orally fed with Rsv (0.75 mg/kg, every 8 h) or normal saline for 4 weeks. Animals were then sacrificed and the brain tissues (hippocampus) processed for biochemical and histological studies. Results: Neurodegeneration and astrocytic activation were noted in the hippocampus of the diabetic rats. TNF-α, IL-6 transcripts and the nuclear NF-κB expression were increased in the brain. In addition, neuropathic alterations in the hippocampus were evident in diabetic rats, including increased blood vessel permeability and VEGF expression, decreased mitochondrial number and AMPK activity. In Rsv-treated diabetic rats, the aforementioned abnormalities were all attenuated. Conclusion: These observations suggest that Rsv significantly attenuated neurodegeneration and astrocytic activation in the hippocampus of diabetic rats. Our results suggested that Rsv could potentially be a new therapeutic agent for diabetic encephalopathy and neurodegeneration.
Neuroendocrinology 03/2013; · 2.38 Impact Factor
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ABSTRACT: Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-κB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.
AJP Endocrinology and Metabolism 07/2011; 301(5):E853-63. · 4.75 Impact Factor
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ABSTRACT: Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte injuries of diabetic kidneys are lessened by RSV.
Chemico-biological interactions 02/2011; 190(1):45-53. · 2.46 Impact Factor
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ABSTRACT: Resveratrol (RSV) has been shown to ameliorate hyperglycaemia and hyperlipidaemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on diabetes mellitus (DM)-induced vasculopathy and explored its possible mechanism.
Male Sprague-Dawley rats were injected with streptozotocin at 65 mg/kg body weight The induction of DM was confirmed by a fasting plasma glucose level > or = 300 mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75 mg/kg body weight three times a day for 4-8 weeks. Animals were sacrificed and vessel wall histology was examined by microscopy. The vascular smooth muscle cell activation was assessed by the medial thickness, collagen deposition, and the expressions receptor for advanced glycation end product, NF-kappaB, proliferation cell nuclear antigen, and the levels of Erk1/2 phosphorylation.
In RSV-treated DM rats, the vascular wall thickening, collagen deposition/cross-linking, and vascular permeability were all alleviated compared with that of the untreated DM rats. The vascular smooth muscle cell of the RSV-treated rats was characterized with less proliferation, lower NF-kappaB, and Erk1/2 activation, decreased proliferation cell nuclear antigen and receptor for advanced glycation end product expression. Moreover, the plasma fructosamine was significantly reduced in RSV-treated DM rats.
RSV alleviated DM-induced vasculopathy through attenuation of advanced glycation end product-receptor for advanced glycation end product-NF-kappaB signalling pathway.
Diabetes/Metabolism Research and Reviews 03/2010; 26(3):212-22. · 3.37 Impact Factor
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Ju-li Wang,
Chong-yang Han, Yu-hong Jing,
Yu-cai Chen,
Nan Feng,
Jian-jun Lu,
Yue-hua Zhang,
Hong Pan,
Hu-sheng Wu,
Ke-ming Xu,
Yu-wu Jiang,
Jian-min Liang,
Ling Wang,
Xiao-liang Wang,
Yan Shen,
Xi-ru Wu
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ABSTRACT: To study the effect of CACNA1H gene mutation G773D on calcium channel function.
By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells.
There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly.
CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 09/2006; 23(4):369-73.
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ABSTRACT: To explore the effects of M3 receptor on myocyte apoptosis induced by acute myocardial infarction in rats.
Rat model was induced by ligation of the anterior branch of the left coronary artery. All animals were divided into four groups: sham-operated group, occlusion group, choline group (10 mg x kg(-1), iv), and 4DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) group (0.12 mg x kg(-1), iv). The serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined. The infarct size areas on the myocardium were identified by TTC staining. The apoptosis in cardiomyocyte was detected by TUNEL assay and apoptosis-related proteins in Bcl-2 and Fas expression were measured by immunohistochemistry assay.
M3 receptor agonist choline reduced serum MDA content and increased SOD activity. The myocardial expression of Bcl-2 was increased, whereas the expression of Fas was decreased by choline. However, blockade of M3 receptor by 4DAMP completely inhibited these effects of choline on cardiac myocytes.
Activation of M3 receptor has protective effect on myocyte apoptosis induced by acute myocardial infarction in rat, and this effect might be related to modulating the expression of some immediateearly genes including Bcl-2 and Fas.
Yao xue xue bao = Acta pharmaceutica Sinica 06/2004; 39(5):338-41.
