Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serratia marcescens is an important nosocomial pathogen, which has been especially problematic as a cause of hospital-acquired pneumonia in the past two decades. Treatment of S. marcescens-related infections has been limited by emergence of multiple drug-resistant strains. Thus, the development of alternative agents for the prevention and treatment of Serratia infection is urgently needed. Resveratrol (RSV) is a compound with diverse biological effects including anti-cancer, anti-inflammation, anti-diabetes, and cancer chemoprevention. Whether RSV has in vivo prophylactic or therapeutic potential against infection remains uncharacterized. In the present study, we used a murine acute pneumonia model initiated by intratracheal application of S. marcescens to evaluate whether RSV possesses anti-infection properties. We showed that pretreatment with RSV for 3 days markedly increased alveolar macrophage infiltration, elevated NK cell activity, and decreased bacterial burden in the infected lung with a subsequent decrease in mortality. These effects were associated with significantly less-severe inflammatory phenotypes in lung tissue and bronchoalveolar lavage fluid, including reduced neutrophil infiltration of the lungs, reduced phagocytosis activity, and reduced secretion of cytokines such as TNF-alpha, IL-1beta, and IL-6. To further characterize the underlying mechanism responsible for these effects of RSV, LPS derived from S. marcescens was used to induce acute pneumonia in rats, with or without RSV pretreatment. RSV was shown to ameliorate acute pneumonia via inhibition of the NF-kappaB signaling pathway, including inhibition of IkappaBalpha phosphorylation and subsequent NF-kappaB activation. These findings suggest that RSV might be beneficial as a prophylactic treatment in patients at risk of an episode of S. marcescens-induced acute pneumonia.
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PMID:Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats. 1817 63

Resveratrol, a naturally occurring phytoalexin, is known to exert numerous beneficial effects in the organism. Literature data indicate that this compound may, among other effects, play a role in prevention of diabetes and diabetic complications. Resveratrol was recently found to affect insulin secretion in vitro and to change blood insulin concentrations. These effects are, however, not fully elucidated. In the present study, 1, 10 and 100microM resveratrol incubated for 90min with pancreatic islets isolated from normal rats failed to affect basal insulin release, but substantially impaired the secretory response to physiological and maximally effective glucose. In depolarized islets exposed to resveratrol, succinate-induced insulin secretion was also diminished. The blockade of somatostatin receptors substantially enhanced insulin secretion induced by 6.7mM glucose and simultaneously suppressed the inhibitory effect of 1microM resveratrol, but at 10 and 100microM, resveratrol was still able to attenuate hormone secretion. Acetylcholine clearly increased the insulin-secretory response to 6.7mM glucose and canceled the inhibitory effect of 1microM resveratrol. However, resveratrol at concentrations 10 and 100microM strongly decreased insulin secretion. The direct activation of protein kinase C totally suppressed the inhibitory influence of 1 and 10microM resveratrol on hormone secretion. However, activation of this enzyme appeared to be insufficient to cancel the insulin-suppressive effect of 100microM resveratrol. These data indicate that resveratrol-induced inhibition of insulin secretion may be partially mitigated by suppression of somatostatin action, activation of protein kinase C or the presence of acetylcholine. The in vivo experiment revealed that resveratrol, administered to normal rats at the dose 50mg/kg body weight, diminished blood insulin concentrations at 30min, without concomitant changes in glycemia. These observations point to the direct insulin-suppressive action of resveratrol in the rat.
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PMID:The insulin-suppressive effect of resveratrol - an in vitro and in vivo phenomenon. 1820 58

Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.
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PMID:Resveratrol: a multitargeted agent for age-associated chronic diseases. 1841 53

Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.
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PMID:The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats. 1845 15

Resveratrol may protect against metabolic disease through activating SIRT1 deacetylase. Because we have recently defined AMPK activation as a key mechanism for the beneficial effects of polyphenols on hepatic lipid accumulation, hyperlipidemia, and atherosclerosis in type 1 diabetic mice, we hypothesize that polyphenol-activated SIRT1 acts upstream of AMPK signaling and hepatocellular lipid metabolism. Here we show that polyphenols, including resveratrol and the synthetic polyphenol S17834, increase SIRT1 deacetylase activity, LKB1 phosphorylation at Ser(428), and AMPK activity. Polyphenols substantially prevent the impairment in phosphorylation of AMPK and its downstream target, ACC (acetyl-CoA carboxylase), elevation in expression of FAS (fatty acid synthase), and lipid accumulation in human HepG2 hepatocytes exposed to high glucose. These effects of polyphenols are largely abolished by pharmacological and genetic inhibition of SIRT1, suggesting that the stimulation of AMPK and lipid-lowering effect of polyphenols depend on SIRT1 activity. Furthermore, adenoviral overexpression of SIRT1 stimulates the basal AMPK signaling in HepG2 cells and in the mouse liver. AMPK activation by SIRT1 also protects against FAS induction and lipid accumulation caused by high glucose. Moreover, LKB1, but not CaMKKbeta, is required for activation of AMPK by polyphenols and SIRT1. These findings suggest that SIRT1 functions as a novel upstream regulator for LKB1/AMPK signaling and plays an essential role in the regulation of hepatocyte lipid metabolism. Targeting SIRT1/LKB1/AMPK signaling by polyphenols may have potential therapeutic implications for dyslipidemia and accelerated atherosclerosis in diabetes and age-related diseases.
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PMID:SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. 1848 75

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD(+)-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes.
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PMID:Sirtuins: novel targets for metabolic disease in drug development. 1857 74

Resveratrol is a polyphenolic phytoalexin produced in appreciable amounts as a secondary metabolite in grapevines in response to fungal infections. Based on the present knowledge, it appears to be a promising bioactive natural molecule with potential applications in phytotherapy or pharmacology. The present study was aimed to evaluate the antidiabetic properties of resveratrol in streptozotocin-nicotinamide induced experimental diabetes in rats. The diabetic rats orally treated with resveratrol (5 mg kg(-)(1)b.w d(-)(1)) for 30 days resulted in significant (p<0.05) decrease in the levels of blood glucose, glycosylated hemoglobin, blood urea, serum uric acid, serum creatinine and diminished activities of pathophysiological enzymes such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). The antihyperglycemic nature of resveratrol is also evidenced from the improvement in the levels of plasma insulin and hemoglobin. Further, the results are comparable with glyclazide, an oral standard drug. Thus, the present findings suggest that resveratrol may be considered as an effective therapeutic agent for the treatment of diabetes mellitus.
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PMID:Resveratrol, a natural phytoalexin, normalizes hyperglycemia in streptozotocin-nicotinamide induced experimental diabetic rats. 1867 32

Resveratrol is a potent member of the class of natural, plant-derived chemicals known as polyphenols. These help explain in part why a diet high in fruit and vegetables confers health benefits and are associated with reduced risk of common complex conditions such as cardiovascular disease, cancer, diabetes, and Alzheimer's disease. We present the latest molecular findings that account for the beneficial actions of resveratrol. The intracellular pathways activated are crucial for anti-oxidant defence, regulation of the cell cycle, mitochondrial energy production, vascular tone, oncogene suppression, and many other phenomena which if unchecked lead to morbidity and mortality from onset and progression of these various diseases. While a healthy diet and lifestyle is strongly recommended in prevention of such conditions, the future bodes well for the use of resveratrol and analogues of higher potency than the natural form for treatment of diseases that afflict humans, particularly as they age.
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PMID:Resveratrol in prevention and treatment of common clinical conditions of aging. 1868 54

Resveratrol, a ubiquitous stress-induced phytoalexin, has demonstrated a wide variety of biological activities which make it a good candidate for the treatment of diabetes mellitus. The present study was aimed to evaluate its therapeutic potential by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. The daily oral treatment of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days demonstrated a significant (p<0.05) decline in blood glucose and glycosylated hemoglobin levels and a significant (p<0.05) increase in plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver and kidney tissues of diabetic rats were significantly (p<0.05) reverted to near normal levels by the administration of resveratrol. Further, resveratrol administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of resveratrol in diabetic rats. The obtained results were compared with glyclazide, a standard oral hypoglycemic drug. Thus, the modulatory effects of resveratrol on attenuating these enzymes activities afford a promise for widespread use for treatment of diabetes in the future.
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PMID:Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. 1905 88

Resveratrol is a stilbene found naturally in various plants with the highest concentration in the skin of grapes and peanuts. The function of this compound in plants is to confer resistance against bacterial and fungal infection. The effects of resveratrol in animals and humans are currently an area of intense investigation. Resveratrol has been shown to have a plethora of health benefits including protection against cardiovascular disease, various cancers, type II diabetes, and also has life extending properties. The beneficial effects of resveratrol in skeletal muscle have been given less attention in the literature compared to other tissues. Therefore, the focus of this review is to highlight the cellular effects of resveratrol in skeletal muscle. Resveratrol has been shown to alter protein catabolism and muscle function, and confer resistance against oxidative stress, injury, and cell death of skeletal muscle cells. The mechanisms underlying these resveratrol-induced adaptations in skeletal muscle are discussed.
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PMID:Cellular effects of resveratrol in skeletal muscle. 1923 12


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