Pancreas Of Diabetic Rats Research Articles

The Valorization of Agro-Wastes and Stevia Leaves as a Sugar Replacer in Cupcake Formulas: Histological and In Vivo Studies on Diabetic Rats

One potential solution to enhance the nutritional value of food while addressing environmental concerns is to use bioactive extracts from agro-waste in the food industry. This study aimed to investigate the effects of replacing sucrose with powders made from Stevia leaves (SLP), banana peels (BPP), and carrot leaves (CLP), as well as their mixtures, in cupcakes. Additionally, the study aimed to determine the impact of these substitutes on alloxan-induced diabetic rats fed the cupcakes. Sensory evaluation revealed that up to 60% of sucrose in the cupcake formula could be replaced without significant changes in sensory attributes. Substituting agro-wastes and SLP increased the protein content from 12.86% to 14.26% and the dietary fiber content from 3.65% to 5.60% compared to the control sample. The treated diabetic groups, particularly those fed cupcakes containing SLP-CLP mixture, showed increased body weight gain % and feed intake, reducing serum glucose levels from 427.5 to 180.8 mg/dL after 28 days. The mix of CLP-SLP had the highest additive effect, indicating a significant reduction in various biochemical parameters, including ALT, AST, albumin, urea, uric acid, creatinine, total cholesterol, triglyceride, and LDL, compared to the positive control. No histopathological alterations were detected in the pancreas and liver of diabetic rats fed cupcakes supplemented with SLP-CLP. However, moderate degenerations were observed in the hepatocytes of diabetic rats fed cupcakes fortified with SLP-BPP.

The effects of hydroxytyrosol on Prdx6 and insulin expression in diabetic rat pancreases.

Diabetes mellitus is a widespread endocrine disease worldwide, accompanying chronic hyperglycemia. In this study, we investigated the effect of hydroxytyrosol, which exerts an antioxidant effect, on the expressions of insulin and peroxiredoxin-6 (Prdx6), which protect cells against oxidative injury in diabetic rat pancreas. This experimental study had four groups with ten animals in each group: control (nondiabetic) group, hydroxytyrosol group [10mg/kg/day intraperitoneal injection (ip) hydroxytyrosol for 30days], streptozotocin group (single ip injection of 55mg/kg streptozotocin), and streptozotocin + hydroxytyrosol group (single ip injection of streptozotocin and ip injection of 10mg/kg/day hydroxytyrosol for 30days). During the experiment, blood glucose levels were measured at regular intervals. Insulin expression was determined by immunohistochemistry and Prdx6 expression was determined by immunohistochemistry and western blot. Immunohistochemistry and western blot results were analyzed by one-way ANOVA with applied Holm-Sidak multiple comparison test, and blood glucose results were analyzed by two-way repeated measures ANOVA with applied Tukey's multiple comparison test. Blood glucose levels on days 21 and 28 were significantly lower in the streptozotocin + hydroxytyrosol group compared with the streptozotocin group (day 21, p = 0.049 and day 28, p = 0.003). Expression of both insulin and Prdx6 were lower in the streptozotocin and the streptozotocin + hydroxytyrosol groups compared with the control and hydroxytyrosol groups (p < 0.001). Insulin and Prdx6 expression in the streptozotocin + hydroxytyrosol group were higher compared with the streptozotocin group (p < 0.001). The immunohistochemical findings of Prdx6 and western blot were the same. In conclusion, hydroxytyrosol, which is an antioxidant compound, increased Prdx6 and insulin expression in diabetic rats. Insulin increased by hydroxytyrosol may have been effective in reducing blood glucose levels. Furthermore, hydroxytyrosol may exert its effect on insulin by increasing Prdx6 expression. Thus, hydroxytyrosol may decrease or prevent several hyperglycemia-dependent complications by increasing the expression of these proteins.

Blood Glucose Level, Langerhans Pancreas and Lipid Profile of Diabetic Rats After Administration of Red Betel, Ginger and Cinnamon Combination Extract.

Previous studies had reported antihyperglycemic activity in vitro, in vivo and in silico of red betel (Piper crocatum) extract, which was associated with its polyphenolic, tannins, alkaloids, and flavonoids compounds. This study aimed to determine blood glucose level, Langerhans pancreas, lipid profile and bodyweight of streptozotocin-induced diabetic rats after administrating red betel combination extract. Red betel combination extract is composed of red betel extract that was combined with ginger and cinnamon extracts. 16 male rats (Sprague Dawley) were divided randomly into two controls groups (Normal and diabetic groups; orally administered with 2 mL of aquadest for 14 days) and two extract groups (diabetic groups; orally administered with red betel combination extract 9 mL/kg BW and 13.5 mL/kg BW). Results showed that the administration of red betel combination extract for 14 days (9 mL/kg BW dosage) decreased the rat's blood glucose level up to 55.42%, which was significantly different (p < 0.05) compared to the rat's blood glucose levels on day 3. While the combination extract (dosages 9 mL/kg BW and 13.5 mL/kg BW) increased the numbers of rat Langerhans islets up to 10.9%-30.6%. The level of rat's blood high-density lipoprotein (HDL) and triglyceride levels in the diabetic control group were significantly different (p < 0.05) compared to that of the diabetic with red betel combination extract and normal groups. The treatment orally with red betel combination extract (various dosages) for 14 days suppressed the weight loss of rats by 10%-11%.

Effect of Bitter-leaf (Vernonia amygdalina) Flavored Non-alcoholic Wheat Beer (NAWB) on, Insulin and GLUT-2 expression in Pancreas of High fat diet/Streptozotocin (HFD/STZ) Induced Diabetic Wistar Rats.

In the management of type 2 diabetes (T2D), dietary intervention has been proposed to be highly effective. This study, therefore, investigated the effect of bitter leaf-flavored non-alcoholic wheat beer (NAWB) on insulin secretion and GLUT-2 expression in the pancreas of STZ-induced diabetic rats. In this study, the rats received a single intraperitoneal injection (i.p.) of STZ (35mg/kg) after being fed a high-fat diet for 14days to induce T2D. The rats were treated with bitter leaf flavored NAWB samples (100%HP- Hops only, 100%BL-Bitter leaf only, 75,25BL- 75% Hops, 25% Bitter Leaf, 50:50BL- 50% Hops:50% Bitter Leaf, and 25:75BL-25%Hops:75% Bitter Leaf) and Acarbose for 14days. The superoxide dismutase, catalase, and glutathione peroxidase activity were also determined. The results from this study showed a correlation between GLUT-2 and Insulin expression. There was an upregulation of Insulin as GLUT-2 expression was upregulated. Furthermore, the treated groups showed better antioxidant activity when compared with the diabetic control. Bitter leaf-flavored NAWB might thus be a good dietary intervention for type 2 diabetics.

Effects of noopept on ocular, pancreatic and renal histopathology in streptozotocin induced prepubertal diabetic rats

ABSTRACT Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats.

Antidiabetic, antihyperlipidemic and protective effects of Gladiolus psittacinus on hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats.

Gladiolus psittacinus (GP) is an important medicinal plant in folk medicine where its corm is used for treatment of diabetes mellitus. Despite this, there is paucity of scientific information to justify its use as antidiabetic drug. Hence, this study was designed to explore antidiabetic, antihyperlipidemic and effects of aqueous extract of Gladiolus psittacinus (AGP) on hyperglycemia-associated oxidative stress in pancreas, kidney and liver of diabetic rats. Diabetes mellitus (DM) was induced in rats using streptozotocin 50mg/kg (i.p.). Normal and diabetic rats were treated orally with AGP once a day for 14days. Antidiabetic effects were evaluated on body weight, fasting blood glucose concentration (FBGC), lipid profiles and serum chemistry. Also, protective effects of AGP were also determined on markers of oxidative stress, antioxidant enzymes and histopathology of pancreas, kidney and liver of diabetic rats. Treatment with AGP emanated to significant decrease of FBGC (552.67-157.33mg/dL), increase in body weight (100.01-133.76g) and positive modulation of lipid parameters in diabetic rats. The alteration in the contents of markers of liver and kidney function were significantly modulated in the diabetic rats upon treatment. Also, oxidative damage and antioxidant depletions in pancreas, kidney and liver were significantly mitigated in treated diabetic rats. Structural aberrations in the histopathology slides of pancreas, kidney and liver were improved upon treatment. It can be concluded that AGP could be used in the treatment of diabetes mellitus and its related ailments, thereby justifying its usage in traditional medicine.

Reduced volume of diabetic pancreatic islets in rodents detected by synchrotron X-ray phase-contrast microtomography and deep learning network

The pancreatic islet is a highly structured micro-organ that produces insulin in response to rising blood glucose. Here we develop a label-free and automatic imaging approach to visualize the islets in situ in diabetic rodents by the synchrotron radiation X-ray phase-contrast microtomography (SRμCT) at the ID17 station of the European Synchrotron Radiation Facility. The large-size images (3.2mm×15.97mm) were acquired in the pancreas in STZ-treated mice and diabetic GK rats. Each pancreas was dissected by 3000 reconstructed images. The image datasets were further analysed by a self-developed deep learning method, AA-Net. All islets in the pancreas were segmented and visualized by the three-dimension (3D) reconstruction. After quantifying the volumes of the islets, we found that the number of larger islets (=>1500 μm3) was reduced by 2-fold (wt 1004±94 vs GK 419±122, P<0.001) in chronically developed diabetic GK rat, while in STZ-treated diabetic mouse the large islets were decreased by half (189±33 vs 90±29, P<0.001) compared to the untreated mice. Our study provides a label-free tool for detecting and quantifying pancreatic islets in situ. It implies the possibility of monitoring the state of pancreatic islets in vivo diabetes without labelling.

Bambusa vulgaris leaves reverse mitochondria dysfunction in diabetic rats through modulation of mitochondria biogenic genes.

There is evidence that mitochondrial dysfunction mediated by hyperglycemia increases the incidence of diabetes and age-related insulin resistance. Thus, maintaining mitochondrial integrity may provide alternative therapeutic approach in diabetes treatment. This study aimed to evaluate the effect of Bambusa vulgaris leaf extract on mitochondrial biogenesis in the pancreas of diabetic rats. 11weeks old male rats (n=30) were purchased, and sorted into the following groups: control, diabetic control, diabetes+metformin (100mg/kg), diabetes+Aq. B.vulgaris (100mg/kg), diabetes+Aq. B.vulgaris (200mg/kg), and diabetes+Aq. B.vulgaris (300mg/kg). Diabetes was induced in the rats by a single dose of 65mg/kg streptozotocin (STZ). The mRNA expression of genes related to mitochondria biogenesis (pgc-1α, Nrf2, GSK3β, AMPK and SIRT2) and genes of Nrf2-Keap1-ARE signaling pathway were determined by reverse transcriptase polymerase chain reaction. Molecular docking studies including lock and key docking and prime MM-GBSA were incorporated to identify the lead chemical compounds in Bambusa vulgari. The results showed that B.vulgaris leaf extract promotes mitochondrial biogenesis via altering the mRNA expression of mitochondrial master regulator pgc-1α, otherupstream genes, and the Nrf2-Keap1-ARE antioxidant pathway. Through molecular docking results, cryptochlorogenic acid, hesperidin, orientin, vitexin, scopolin, and neochlorogenic were found as the crucial chemicals in B.vulgaris with the most modulating effect on PGC-1α, AMPK, and GSK3. This study thus suggests that B.vulgaris leaf extract restores the integrity of mitochondria in diabetic rats.

Attenuation of the cytotoxic, nephrotoxic and hepatotoxic effects of streptozotocin-induced diabetic rats by aqueous extract of Lepidium sativum L. (Brassicaceae)

Diabetes mellitus is a health condition whose major feature is hyperglycemia that arises from various etiologies. Diabetes mellitus is connected with constraints in the metabolism of proteins and lipids which leads to complications such as hepatopathy, nephropathy, retinopathy and vasculopathy. Plant resources are utilized for better beneficial curative molecules, minimal side effects and cost. Lepidium sativum (garden cress) is a plant whose parts have been reportedly employed in the treatment of conditions like inflammation, diabetes, pyretism, hemorrhage and hypertension. This histopathological study sought to investigate the effect of the aqueous extract of L. sativum on the tissues of the pancreas, kidney, and liver in streptozotocin-induced diabetic rats. Haematoxylin and Eosin Staining method of histopathology was employed and the cytotoxic, nephrotoxic and hepatoxic effects on the pancreatic Islet cells, kidney and liver were attenuated on treatment with different doses of aqueous extracts of L. sativum plant.

Antioxidant properties of date seeds extract (Phoenix dactylifera L.) in alloxan induced damage in rats.

The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the liver, kidney, and pancreas in diabetic's rats. Group 1: control group, that did not receive any treatment, Group 2: alloxan was injected intraperitoneally (120 mg/kg body weight) for two days (Diab), Group 3: treated only by date seeds powder added in the diet (300 g/kg) for 6 weeks (DSPK), Group 4: alloxan-diabetic rats treated with date seeds powder (300 g/kg) (DSPK + Diab). Estimations of biochemical parameters in blood were determined. TBARS, SOD, CAT, and GPx activities were determined. A histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin hematoxylin-eosin staining. In addition, the antioxidant activities of DSPK were evaluated by DPPH radical scavenging activity, reducing power, and ABTS free radical scavenging. The results revealed that date seeds significantly decreased serum levels of glucose, cholesterol, triglycerides, urea, creatinine, T-protein, ALP, D-bili and T-bili levels. In addition, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities that had been reduced in liver, kidney, and pancreas of the treated group were restored by DSPK treatments and, therefore, the lipid peroxidation level was reduced in the liver, kidney and pancreas tissue compared to the control group. Additionally, the histological structure in these organs was restored after treatment with date seeds powder.

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats

BackgroundNowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE.MethodsFirstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days.ResultsThe results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress.ConclusionCo-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Exercise alleviates diabetic complications by inhibiting oxidative stress-mediated signaling cascade and mitochondrial metabolic stress in GK diabetic rat tissues.

Type 2 diabetes, obesity (referred to as "diabesity"), and metabolic syndrome associated with increased insulin resistance and/or decreased insulin sensitivity have been implicated with increased oxidative stress and inflammation, mitochondrial dysfunction, and alterations in energy metabolism. The precise molecular mechanisms of these complications, however, remain to be clarified. Owing to the limitations and off-target side effects of antidiabetic drugs, exercise-induced control of hyperglycemia and increased insulin sensitivity is a preferred strategy to manage "diabesity" associated complications. In this study, we have investigated the effects of moderate exercise (1h/day, 5days a week for 60days) on mitochondrial, metabolic, and oxidative stress-related changes in the liver and kidney of type 2 diabetic Goto-Kakizaki (GK) rats. Our previous study, using the same exercise regimen, demonstrated improved energy metabolism and mitochondrial function in the pancreas of GK diabetic rats. Our current study demonstrates exercise-induced inhibition of ROS production and NADPH oxidase enzyme activity, as well as lipid peroxidation and protein carbonylation in the liver and kidney of GK rats. Interestingly, glutathione (GSH) content and GSH-peroxidase and GSH reductase enzymes as well as superoxide dismutase (SOD) activities were profoundly altered in diabetic rat tissues. Exercise helped in restoring the altered GSH metabolism and antioxidant homeostasis. An increase in cytosolic glycolytic enzyme, hexokinase, and a decrease in mitochondrial Kreb's cycle enzyme was observed in GK diabetic rat tissues. Exercise helped restore the altered energy metabolism. A significant decrease in the activities of mitochondrial complexes and ATP content was also observed in the GK rats and exercise regulated the activities of the respiratory complexes and improved energy utilization. Activation of cytochrome P450s, CYP 2E1, and CYP 3A4 was observed in the tissues of GK rats, which recovered after exercise. Altered expression of redox-responsive proteins and translocation of transcription factor NFκB-p65, accompanied by activation of AMP-activated protein kinase (AMPK), SIRT-1, Glut-4, and PPAR-γ suggests the induction of antioxidant defense responses and increased energy metabolism in GK diabetic rats after exercise.

The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.

The goal of this study was to see how effective subcutaneous (SC) insulin is and two different types of oral insulin-loaded nanoparticles (INS) including carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) separately and compare their effects on glucokinase, pyruvate kinase gene expressions, and other parameters in diabetes type one male Wistar rats. Seven groups of ten male Wistar rats for each group were formed at random including four control groups (n= 10) and three treatment groups (n= 10). The control groups consisted of four control groups (10 rats for each) and three treatment groups (10 rats for each). Normal control rats were not given any treatment, as were diabetic rats that were not given any treatment, and diabetic rats that were given oral nanoparticles (CMCNPs and AuNPs). Diabetic rats were given subcutaneous insulin, oral insulin-loaded carboxymethyl chitosan nanoparticles (INS-CMCNPs), and oral insulin-loaded gold nanoparticles (INS-AuNPs). The rats were treated for the final 3 weeks of the experiment, which lasted 4 weeks. CMCNPs and AuNPs presented a promising effect on pyruvate kinase and Glucokinase gene expressions compared to subcutaneous insulin. We also discovered that conjugating insulin to CMCNPs and AuNPs protects them from the insulin-degrading enzyme, which offers managed bioavailability. Furthermore, we investigated the effects of CMCNPs and AuNPs on several parameters and discovered that both have a significant effect in vivo, which enables glucose level regulation, and improves patient organ activity for better glucose consumption. PRACTICAL APPLICATIONS: In this paper, we discussed the effect of oral INS-CMCNPs and INS-AuNPs, and compared their effects on Glucokinase and pyruvate kinase gene expressions and other biochemical parameters in diabetes type one male Wistar rats. On the other hand, we investigated the impact of oral INS and subcutaneous insulin separately on the same parameters and their effect on the histology of the liver and pancreas of diabetic rats. According to our research, as we discussed the different mechanisms of INS-CMCNPs and INS-AuNPs, they presented a promising effect compared to SC insulin. They can be used to keep oral insulin safe from the environment of the gastrointestinal system to overcome all the barriers, improve the therapeutic, and clinical outcomes of insulin by maintaining its desired concentration inside the body, ending the panic of the patient from receiving insulin by the SC injection by increasing his satisfaction with receiving accurate oral insulin doses.

Activity fingerprinting of polysaccharides on oral, gut, pancreas and lung microbiota in diabetic rats

The modern rise in type 2 diabetes mellitus (T2DM) and its correlation to commensal microbiota have elicited global concern about the patterns of microbial action in the host. With the exception of that linked to gut, microbiota were also colonized in pancreas, oral, and lung, contributing to the physiopathology of T2DM. In this study, we aimed to explore the protective effects of Ganoderma atrum polysaccharide (PSG) and White Hyacinth Bean polysaccharide (WHBP) on the intestine, pancreas, oral, and lung microbiota in T2DM rats. Here we showed that, despite capacities of polysaccharides that exerted similar protective effects on hyperglycemia, dyslipidemia, insulin resistance and dysbacteriosis in T2DM rats, PSG and WHBP were able to be characterized by their own "target" bacteria, which could be proposed for activity-fingerprinting of polysaccharide species. Furthermore, we found a mutual bacteria spectrum in the pancreas and lung, and most bacteria could be tracked to oral or gut samples. Notably, the overlapping areas of the microbiota profile between organs (pancreas, lung) and saliva were more than in the gut, suggesting that a saliva sample was also of interest to serve as a "telltale sign" for judging pancreatic injury. Together, these microbiota interactions provided a new potential to harvest alternative samples for disease surveillance. Meanwhile, polysaccharides had anti-T2DM abilities, which could be distinguished by their own characteristic bacteria.

Expression Profiling of Pdx1, Ngn3, and MafA in the Liver and Pancreas of Recovering Streptozotocin-Induced Diabetic Rats.

Studies in animal diabetic models have demonstrated the possibility of islet regeneration through treatment with natural extracts, such as Allium sativum (garlic). This study aimed to investigate the effect of garlic extract (GE) on the expression of three genes (Ngn3, Pdx1, and MafA) in the pancreas and liver of diabetic rats. Thirty-two rats were divided into two groups, streptozotocin (STZ)-induced diabetic rats (n = 16) and healthy rats (n = 16). Both groups were subdivided into GE-treated (n = 8), and those administered 0.9% normal saline (NS) (n = 8) for 1 week (n = 4) and 8 weeks (n = 4). In the pancreas of diabetic rats treated with GE for 1 week, all three genes, Ngn3, Pdx1, and MafA, were significantly upregulated (p ≤ 0.01, p ≤ 0.05, and p ≤ 0.001, respectively) when compared to diabetic rats treated with NS only. However, after eight weeks of GE treatment, the expression of all three genes decreased as blood insulin increased. In the liver, only Pdx1 expression significantly (p ≤ 0.05) increased after 8 weeks. The significant expression of Ngn3, Pdx1, and MafA in the pancreas by week 1 may have induced the maturation of juvenile β-cells, which escaped the effects of STZ and caused an increase in serum insulin.

Effect of Eight Weeks of Endurance Training in Light and Dark Phases of Circadian Rhythm on the Oxidative Stress Index in Pancreas of Diabetic Mice

Introduction: Chronic hyperglycemia is associated with an increase in cellular damage due to oxidative stress in pancreatic tissue. The effect of exercise in different phases of the circadian cycle on protecting pancreatic tissue from oxidative stress in diabetic patients is unknown. The aim of this study was to investigate the effect of eight weeks of endurance training in light and dark phases of circadian rhythm on the oxidative stress index in pancreas of diabetic mice.&#x0D; Methods: In this study, 18 mice from the Naval Medical Research Institute (26.3±3.22 gr) were selected and after inducing diabetes through high-fat food and Streptozotocin injection (20 mg/kg), randomly divided into 6 groups: light phase healthy control, dark phase healthy control, light phase diabetic control, dark phase diabetic control, light phase diabetic training and dark phase diabetic training. The endurance training protocol (50-60 %Vmax) was performed 5 d/w for 8 weeks. After anesthesia, blood samples and pancreatic tissues were removed. Insulin resistance markers, oxidative stress index and expression of Brain and Muscle ARNT-Like1 protein expression were measured in pancreas of diabetic rats. Data were analyzed by one way analysis of variance at the significance level of p &lt;0.05.&#x0D; Results: The eight weeks of endurance training significantly decreased insulin resistance markers (p= 0.005), oxidative stress index (p ˂0.05) and significantly increased the Bmal1 protein expression (p = 0.009). The mean values of all variables showed significant differences between light and dark phases.&#x0D; Conclusion: Endurance training may improve insulin sensitivity and oxidant damage in diabetic conditions by increasing the function of the antioxidant system and the expression of Circadian regulation proteins. Activity in the dark phase causes further increases the metabolism of cells. As a result, performing these types of exercises in the dark phase is recommended to these patients as a new treatment strategy.

Evaluation of Hypoglycemic and Hypolipidemic Activities of Methanolic Leaf Extract of Garcinia gummi-gutta Linn by HFD with Low Dose STZ Induced Type II Diabetes Mellitus on Rats

Objective: The present study aimed to evaluate the hypoglycemic and hypolipidemic activities of methanolic leaf extract of Garcinia gummi-gutta Linn. by HFD with low dose STZ induced T2DM on rats.&#x0D; Materials and Methods: The animals were divided into five groups of six animals, and HFD was induced for 8 weeks. After 4th week of HFD treatment, type-II diabetes was induced by a single dose of 35mg/kg (i.p) STZ, hyperglycemia was confirmed by the elevated levels of blood glucose determined at 72h and the animals with blood glucose concentration (&lt; 250mg/dl) were used for the study. The In vitro anti-diabetic activity was done by the DNS method.&#x0D; Results: The In vitro anti-diabetic activity by α-amylase inhibition activity by DNS method was very mild as compared to Acarbose and the IC50 value of Acarbose was very low (170.84µg/ml) than MEGG (1989.59µg/ml). However, potent In vivo anti-diabetic activity (P&lt;0.001) was observed after induction HFD with low dose STZ induced T2DM rats at the end of the 8th week, blood sugar level for MEGG high dose (173.40 ± 14.9mg/dl) was found to be almost same as that of standard drug Glibenclamide (164.60 ± 3.21mg/dl) as compared to control (287.90 ± 1.52). The lipid profile of the study showed a marked increase in TC, LDL, TG, and reduction in HDL in HFD with low dose STZ diabetic rats, whereas in MEGG and standard drugs treated by Glibenclamide were found to be substantially decreased and a fair amount of improvement in HDL level (P&lt;0.001). Histologically, focal necrosis was observed in the diabetic rat pancreas whereas on standard and test mild and no evidence of necrosis were observed respectively, similar positive results were found in liver and adipocyte histology for standard and test groups against the HFD with STZ-induced group&#x0D; Conclusion: Therefore MEGG possesses potent In vivo anti-diabetic effect as well as hypolipidemic effect and therefore MEGG might be a potent phytochemical alternative to prevent and treat T2DM and atherosclerosis and also to reduce its associated complications.

Anti Diabetetic Activity of Illupai Ver Chooranam on Streptozotocin Diabetic Rats

Roots of Illupai (Madhuca longifolia) are mentioned for Madhumegam in Gunapadam -Mooligai (Siddha Materia Medica). The disease Madhumegam found in siddha text is correlated with Diabetes mellitus type-II. Madhuca longifolia known as Illupai in Tamil has been widely used for the treatment of diabetes. Hence, the present study aimed to demonstrate the antidiabetic effects of Illupai ver chooranam in normal and streptozotocin (STZ) induced diabetic rats. The qualitative phytochemical analysis of the chooranam showed the presence of flavonoids, glycosides, tannins, triterpenoids, polyphenols, carbohydrates, steroids, saponin and proteins. Acute toxicity studies revealed the nontoxic nature of the illupai ver chooranam up to a dose level 2000 mg/kg body weight until the end of the study period. The illupai ver chooranam (500 and 1000 mg/kg) significantly reduced (P**&lt; 0.01) glucose levels in diabetic rats. The other biochemical parameters like cholesterol, lipid, urea, protein, liver glycogen, serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT), were found to be reduced by the illupai ver chooranam. The histopathological results of treated groups showed the regenerative/protective effect on cells of pancreas in diabetic rats. In the oral glucose tolerance test, the illupai ver chooranam increased the glucose tolerance. The current study revealed the antidiabetic potential of illupai ver chooranam effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use.

Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats

Ethnopharmacological relevancePsidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa.Aim of the study: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. Material and methodsPhytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250–300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. ResultsIn the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes’ activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. ConclusionCollectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

Methanolic Leaf Extract of Dryopteris dilatata Reverses Kidney Injury on Streptozotocin-Induced Diabetic Male Wistar Rats

Background: Hyperglycemia when sustained leads to diabetes which has become a chronic disorder having morbidity and mortality rate. This study investigated the effect of methanolic leaf extract of Dryoptersis dilatata (MEDd) on kidney injury caused on streptozotocin (STZ)-induced diabetic Wistar rats. Materials and Methods: Thirty Wistar rats were divided into five groups of six rats each. Group 1 received distilled water (10 ml/kg); Group 2 received STZ (60 mg/kg) only, Groups 3 and 4 received STZ followed by 400 and 800 mg/kg of MEDd, respectively, while Group 5 received STZ + Pioglitazone (10 mg/kg). After 2 weeks of treatment, rats were sacrificed and blood, spleen, liver, pancreas, and kidney were collected for biochemical analysis. Results: The results showed that MEDd extract caused a significant decrease (P &lt; 0.05) in STZ-induced diabetic rats, oxidative stress markers, malondialdehyde nitric oxide, and glutathione superoxide were ameliorated in organs such as the kidney and pancreas in diabetic rats after treatment with MEDd. Kidney markers (urea and creatinine) were ameliorated as well as reduction in organ weights in diabetic rats following treatment with MEDd. Conclusion: Therefore, it was observed from our study that MEDd has antidiabetic and nephron-protective capacity as it ameliorates in vivo adopted in lieu of nephropancreatic caused by STZ-induced diabetes.