Influence of heme oxygenase-1 gene transfer on the viability and function of rat islets in<i>in vitro</i>culture

Chen, Xiaobo; Li, Yongxiang; Jiao, Yang; Dong, Wei; Li, Ge; Chen, Jing; Tan, Jianming

doi:10.3748/wjg.v13.i7.1053

Cited by 19 publications

(12 citation statements)

References 32 publications

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“…Because the protective role of HO-1 in pancreatic islets that are exposed to high glucose concentration has been reported (44). In addition, in vitro HO-1 gene transfer has been shown to influence the viability and function of rat islets (45). Therefore our reports support the positive role played by resveratrol in glucose regulation and cardioprotection in diabetic myocardium by increasing HO-1 expression.…”

Section: Discussionsupporting

confidence: 65%

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

Thirunavukkarasu

Penumathsa

Koneru

et al. 2007

Free Radical Biology and Medicine

255

212

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Aim-Excessive oxidative stress has been implicated in the pathology and complications of diabetes, which leads to myocardial ischemia reperfusion injury. The present study was designed to examine whether resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenolic compound present in red wine has a direct cardioprotective effect on diabetic myocardium.Methods-Resveratrol (2.5mg/kg b.wt/day) and L-NAME (25mg/kg b.wt/day) were administered orally for 15 days to streptozotocin (65mg/kg) induced diabetic rats. Sprague Dawley rats were divided into 5 groups i) Control ii) Diabetic iii) Diabetic+resveratrol iv) Diabetic+Resveratrol+L-NAME (nitric oxide synthase inhibitor), v) Diabetic+L-NAME. In our present study resveratrol demonstrated significant reduction in glucose level in diabetic rats. After the treatment, the hearts were excised and subjected to 30 min of global ischemia followed by 2 hours of reperfusion.Results-Resveratrol treated diabetic rats demonstrated significant reduction in glucose levels as compared to the non treated diabetic animals, improved left ventricular function throughout reperfusion compared to the diabetic or L-NAME treated animals (dp/dt max 1457 ± 51 vs 999 ± 44 mmHg/sec at 120 min reperfusion). Cardioprotection from ischemic injury in resveratrol treated diabetic rats showed decreased infarct size (42% vs 51%) and cardiomyocyte apoptosis (35% vs 40%) by TUNEL assay. Resveratrol produced significant induction of p-AKT, p-eNOS, Trx-1, HO-1 and VEGF in addition with increased activation of Mn-SOD activity in diabetic animals compared to non-diabetic animals. However treatment with L-NAME in resveratrol treated and non-treated diabetic animals demonstrated significant downregulation of the above mentioned protein expression profile and MnSOD activity. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HO-1 and VEGF in addition with increased MnSOD activity and reduced blood glucose level. Thus this study shows a novel mechanism of pharmacological preconditioning with resveratrol in the diabetic myocardium. Conclusion-In NIH Public Access

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Section: Discussionsupporting

confidence: 65%

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

Thirunavukkarasu

Penumathsa

Koneru

et al. 2007

Free Radical Biology and Medicine

255

212

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“…Furthermore, the overexpression of intracellular antioxidant enzymes and proteins [68] , as well as transgenic islets [15] has been found to improve the function of islets, which is in agreement with our conclusions.…”

Section: Discussionsupporting

confidence: 82%

“…Various strategies such as modifications in enzymatic digestion [13] , purification with iodixanol instead of ficoll [14] , incubation of purified islets in culture medium, genetic manipulation for overexpression [15,16] or silencing [17] of specific genes, employment of different anti-inflammator y or other supplements such as small intestinal submucosa [18] and serecin [19] have been considered in an attempt to increase islet quality and yield. In a previous publication we hypothesized that using phototherapy could improve islet function before transplantation [20] .…”

Section: Islet Isolation and Role Of Oxidative Stressmentioning

confidence: 99%

Islet transplantation and antioxidant management: A comprehensive review

Monfared¹,

Larijani

Abdollahi

2009

WJG

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Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008.All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insufficient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefits of antioxidants in islet isolation procedures cannot be ignored.

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“…About 250-400 islets were yielded from each pancreas. The purity of islets was evaluated by dithizone (DTZ, Sigma, St Louis, MO, USA) staining [16] , and the viability was assessed according to the acridine orange/propidium iodide (AO/PI, Sigma, St Louis, MO, USA) fluorescent staining method [17] . Freshly isolated islets were first cultured overnight at 37℃ in a 50 mL/L CO 2 -950 mL/L air atmosphere in serum-free RPMI 1640 (Hyclone, Gaithersburg, MD, USA) containing 2% (w/v) bovine serum albumin fraction Ⅴ (BSA, Amresco, TX, USA), 11.1 mmol/L glucose, 5 mmol/L glutamine, 1 mmol/L sodium pyruvate, 100 IU/mL pennicillin, 100 μg/mL streptomycin and 15 mmol/L HEPES.…”

Section: Islet Isolation and Culture Conditionsmentioning

confidence: 99%

Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity

Wang¹,

Lu²,

Leng³

et al. 2008

WJG

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AIM:To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism. METHODS: Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 μmol/L) of berberine or 1 μmol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4α ) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4α in the islets. Glucokinase (GK) activity was measured by spectrophotometric method. RESULTS: Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 μmol/L. Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4α expression or GK activity. CONCLUSION: Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4α and GK, which is distinct from sulphonylureas (SUs).

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Influence of heme oxygenase-1 gene transfer on the viability and function of rat islets inin vitroculture

Abstract: The viability and function of rat islets decrease over time in in vitro culture, and heme oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.

Cited by 19 publications

References 32 publications

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

Islet transplantation and antioxidant management: A comprehensive review

Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity

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