Oxidative Stress In Pancreatic Cells Research Articles

Crocin Improves Oxidative Stress by Potentiating Intrinsic Anti-Oxidant Defense Systems in Pancreatic Cells During Uncontrolled Hyperglycemia

IntroductionOxidative stress (OS) during uncontrolled hyperglycemia has a pivotal role in pancreatic dysfunction. Our study aimed to demonstrate that crocin can potentiate anti-oxidant defense systems of pancreatic cells to improve oxidative stress.MethodsMale Wistar rats were divided randomly into four groups: a normal group, a normal-treated group, a diabetic group and a diabetic-treated group (n = 6 rats per group). Diabetes was induced by a single dose of streptozotocin (45 mg/kg/IV). The treated groups received crocin daily for 8 weeks (40 mg/kg/IP). At the end of the experiment, rats were sacrificed and pancreas tissue was obtained. Subsequently, the concentrations of malondialdehyde (MDA), nitrate and glutathione as well as the enzymatic activities of catalase and superoxide dismutase (SOD) were determined in all animals. Data were analyzed by two-way ANOVA with appropriate post hoc testing and a probability value of P < 0.05 was considered to represent a statistically significant difference in mean values.ResultsUncontrolled hyperglycemia weakened the anti-oxidant system by decreasing SOD and catalase enzyme activity in pancreatic tissues and induced OS by increasing the MDA content in diabetic non-treated animals. Crocin potentiated the anti-oxidant defense system by increasing the activity of both SOD and catalase, and improved OS by diminishing MDA production in pancreatic cells of rats contained in the diabetic-treated group.ConclusionBased on our results, it is concluded that uncontrolled hyperglycemia can weaken the anti-oxidant defense system and cause the development of OS. Also, crocin can improve OS in pancreatic cells by potentiating the anti-oxidant defense system.

Effect of Alpha Lipoic Acid on Apoptotic Mechanisms and Oxidative Stress in Pancreatic Cells of High Fat Diet Induced Type II Diabetes Mellitus in Rats

AbstractBackground: Type 2 Diabetes Mellitus (T2DM) is a worldwide health problem with significant morbidity and mortality. b-cell failure is a main contributor to the develop-ment of T2DM. Oxidative stress and enhanced apoptosis play a critical role in pathogenesis of b-cell failure. Recently, Alpha Lipoic Acid (ALA), a universal antioxidant, has been shown to exert anti-apoptotic actions.Aim of Study: The present study was aimed to evaluate the possible ameliorative effect of ALA against pancreatic tissue oxidative stress and apoptotic mechanisms in a rat model of High Fat Diet (HFD)-induced T2DM.Material and Methods: Eighty albino rats were included, 20 rats received a standard diet and served as normal control group (Group I) and 60 rats were fed a homemade HFD for 6 months for induction of T2DM, only diabetics (40 rats) were included and divided into 2 groups; 20 continued to receive HFD for further 21 days, served as diabetic untreated group (Group II); 20 received ALA (50mg/kg i.p) for 21 days and served as ALA-treated group (Group III). Thioredoxin Interacting Protein (TXNIP) and cyclic Adenosine Monophos-phate (cAMP) were immunoassayed in addition to determina-tion of levels of plasma fructosamine, fasting blood glucose (FBG) and pancreatic tissue Malondialdehyde (MDA) along with pancreatic catalase and Superoxide Dismutase (SOD) activities.Results: ALA treatment showed significant improvement in fructosamine and FBG levels, decreased MDA level and increased catalase and SOD activities, in addition to increased cAMP level and decreased TXNIP level.Conclusion: We concluded that ALA has the ability to interfere with b-cell dysfunction associated with HFD-induced T2DM possibly by improving redox status, rescuing cAMP signaling and decreasing the level of TXNIP.

PPAR-α Agonist Improves Hyperglycemia-Induced Oxidative Stress in Pancreatic Cells by Potentiating Antioxidant Defense System

Diabetes-induced oxidative stress has an essential role in pancreatic cells dysfunction. The present study aimed to evaluate whether peroxisome proliferator activated receptor- alpha (PPAR-α) induction by fenofibrate counterbalances oxidative stress in pancreatic cells. In this in vivo study, male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated groups (n=6 in each group). Diabetes was induced by a single intravenous injection of streptozotocin (45 mg/kg). Treated animals received fenofibrate for 8 weeks (80 mg/kg/day) orally. At the end of the 8th week, rats were sacrificed and blood samples and pancreas tissues were collected. Then, the content of malondialdehyde (MDA), nitrate (Nox) and glutathione (GLT) and enzymatic activities of catalase (CAT) and superoxide dismutase (SOD) were assessed. D ata were analyzed using two-way ANOVA. Diabetes deteriorated anti-oxidant defense capacity in pancreatic cells by reducing SOD and CAT activities and induced oxidative stress as reflected by increased MDA content and free radicals production (Nox content). Treatment by fenofibrate increased SOD and CAT activities and improved oxidative stress by decreasing pancreatic MDA and Nox levels. Uncontrolled hyperglycemia weakens anti-oxidant defense capacity in pancreatic cells and contributes to oxidative stress. PPAR-α induction by fenofibrate can restore anti-oxidant defense systems and improve diabetes-induced oxidative stress.

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells.

Insulin resistance results from impaired insulin signaling in target tissues that leads to increased levels of insulin required to control plasma glucose levels. The cycle of hyperglycemia and hyperinsulinemia eventually leads to pancreatic cell deterioration and death by a mechanism that is yet unclear. Insulin induces ROS formation in several cell types. Furthermore, death of pancreatic cells induced by oxidative stress could be potentiated by insulin. Here, we investigated the mechanism underlying this phenomenon. Experiments were done on pancreatic cell lines (Min-6, RINm, INS-1), isolated mouse and human islets, and on cell lines derived from nonpancreatic sources. Insulin (100nM) for 24h selectively increased the production of ROS in pancreatic cells and isolated pancreatic islets, but only slightly affected the expression of antioxidant enzymes. This was accompanied by a time- and dose-dependent decrease in cellular reducing power of pancreatic cells induced by insulin and altered expression of several ER stress response elements including a significant increase in Trb3 and a slight increase in iNos The effect on iNos did not increase NO levels. Insulin also potentiated the decrease in cellular reducing power induced by H2O2 but not cytokines. Insulin decreased the expression of MCL-1, an antiapoptotic protein of the BCL family, and induced a modest yet significant increase in caspase 3/7 activity. In accord with these findings, inhibition of caspase activity eliminated the ability of insulin to increase cell death. We conclude that prolonged elevated levels of insulin may prime apoptosis and cell death-inducing mechanisms as a result of oxidative stress in pancreatic cells.

Resveratrol protects RINm5F pancreatic cells from methylglyoxal-induced apoptosis

The effects of resveratrol on the prevention of apoptosis as well as insulin production are unclear. To examine the effects, we treated insulin-secreting beta cells with methylglyoxal (MG), a metabolite known to induce apoptosis and diabetes in the presence or absence of resveratrol. The MG treatment induced the expression of apoptotic signaling molecules and decreased insulin production. Pretreatment with resveratrol resulted in an increase in insulin synthesis via upregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) and pancreatic-duodenal homeobox-1 (PDX-1). Resveratrol also inhibited MG-mediated expression of CCAAT/enhancer-binding protein beta (C/EBPbeta), a negative regulator of insulin production. Moreover, resveratrol strongly activated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which resulted in the attenuation of oxidative stress. These results suggest that resveratrol can attenuate MG-induced oxidative stress in pancreatic cells and increase insulin levels.