Pancreas Of Diabetic Rats Research Articles

68Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma

ObjectiveGlucagon-like peptide-1 receptor (GLP1R) specifically expressed on the surface of pancreatic β-cells and insulinoma, is a potential biomarker for imaging β-cell mass (BCM). In this study, two new 68Ga-labelled GLP1R targeting agents were prepared and their biological properties for imaging BCM and insulinoma were evaluated. Methods[68Ga]Ga-HBED-CC-MAL-Cys39-exendin-4 ([68Ga]Ga-4) and its dimer ([68Ga]Ga-5) were synthesized from corresponding precursors. Cell uptake studies were evaluated in INS-1 cells. Biodistribution and microPET studies were performed in male normal Sprague-Dawley rats, diabetic rats and insulinoma xenograft NOD/SCID mice. Results[68Ga]Ga-4 and [68Ga]Ga-5 were efficiently radiolabelled by a simple one-step reaction without purification leading to high radiochemical yields and radiochemical purities (both >95%, decay corrected, n = 6, molar activity 15 GBq/μmol). They both showed excellent stability (~95%) in phosphate-buffered saline, pH 7.4, and in rat serum (~90%) for 2 h. Biodistribution studies and small animal PET/CT imaging showed that [68Ga]Ga-4 displayed specific uptake in rat pancreas and mouse insulinoma, and a reduced uptake in the pancreas of diabetic rat was observed (~62% reduction). Notably, it exhibited a rapid time-to-peak pancreatic uptake (0.96 ± 0.19%ID/g in 15 min) and fast clearance from the kidney (42% clearance in 30 min). Results suggested a favorable in vivo kinetics for human imaging studies. Conclusions[68Ga]Ga-4 targeting GLP1R of pancreatic β-cells may be a potentially useful PET agent and a suitable candidate for further structural modification studies. This agent has demonstrated several advantages, rapid time-to-peak pancreatic uptake and faster clearance from the kidney, factors may enhance diagnosis of diabetes and insulinoma.

TRPV1 Receptor-Mediated Hypoglycemic Mechanism of Capsaicin in Streptozotocin-Induced Diabetic Rats.

Our previous research showed that capsaicin exhibits hypoglycemic effects by activating the transient receptor potential vanilloid 1 (TRPV1) channel in diabetic rats. Interestingly, capsiate was also able to activate the TRPV1 channel, but with a non-significant hypoglycemic effect. This study aimed to investigate the effect of capsaicin on the glycometabolism of streptozotocin (STZ)-induced diabetic rats by blocking the TRPV1 channel. After a 4-week capsaicin treatment (6 mg/kg·bw), the serum insulin level of STZ-induced diabetic rats increased from 15.2 to 22.1 mIU/L, the content of hepatic glycogen and muscle glycogen increased by 81.2 and 20.2%, respectively, and the blood glucose level decreased significantly from 19.3 to 14.7 mmol/L. When the TRPV1 channel was blocked, capsaicin lost the above-mentioned effects, and the hypoglycemic effect was no longer significant. It was concluded that a combined up-regulation of both TRPV1 receptors and pancreatic duodenal homeobox-1 (PDX-1) led to the hypoglycemic effect of capsaicin, which partially explains our previous observation: capsiate activating TRPV1 without showing a significant hypoglycemic effect was due to the lack of a significant up-regulation of PDX-1. Based on the experimental results, we speculated that two signaling pathways [TRPV1-(PDX1)-(GLUT2/GK) and TRPV1-(PDX-1)-(IRS1/2)] exist in the pancreas of STZ-induced diabetic rats.

Effect of Aspirin on Mitochondrial Dysfunction and Stress in the Pancreas and Heart of Goto-Kakizaki Diabetic Rats.

Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.

The effect of functional rice analogue diet from mocaf, corn, pigeon pea and seaweed on rats model of type 2 diabetes

Rice analogue (RA) consisting of mocaf, corn, pigeon pea and seaweed from East Lombok, Indonesia was formulated into a low glycaemic index (GI) alternative food. The effect of this RA to control diabetes mellitus (DM) on blood glucose, insulin serum and histology of the pancreas was assayed by in vivo experiment using male and female rats aged 10 weeks that had been induced by streptozotocin (STZ) 90 mg/kg body weight 2 days after birth. The treatment was given for 14 days and compared with Broiler-1 (BR-1) feed. The GI test showed that RA has a low GI (47.36), while BR-1 has a moderate GI (66.35). The blood glucose of the RA group was significantly decreased (p<0.05), while insulin serum was increased in comparison to this of BR-1. Histological observation showed an improvement in the pancreas of diabetic rats after treatment with RA in comparison to this of BR-1. The immunohistochemistry (IHC) assay showed an increase in insulin expression in RA-treated diabetic rats. This study concluded that RA has a low GI. The products were able to increase serum insulin, improve morphological Langerhans and insulin expression on rats model of type 2 DM.

Anti-diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat

The ever-increasing use of plant-based pharmaceuticals as alternatives to conventional drugs for disease management demands identification, isolation, and characterization of novel compounds. Despite the potential of plant extracts to mitigate the morbidity of diseases, several active principles are preferred to avoid the interference of other compounds. The promising health benefits of the extracts and isolated compounds of Pterocarpus santalinus in the treatment of diabetes, cardiovascular disease, cancer, and infections have been described. However, such studies on the active principle, namely, santalins, are not reported. In this study, we standardized the isolation of a mixture of santalins A and B from the heartwood of P. santalinus by column chromatography followed by preparative TLC and HPLC. The partially purified santalins were characterized by LC-MS, HR-MS, and 1 H NMR analyses. The isolated combination of santalins displayed higher total antioxidant and DPPH free radical scavenging activity in vitro than the crude heartwood extracts. Administration of the mixture of santalins A and B did not exhibit any antihyperglycemic activity in the liver, kidney, and pancreas of alloxan-induced diabetic rats. However, pretreatment of rats with a mixture of santalins at a dose of 1.0 mg/kg body weight prevented alloxan-induced diabetes as indicated by the normal blood glucose levels. Hyperglycemia-associated lipid peroxidation was abrogated in santalin-pretreated rats that did not develop alloxan-induced diabetes. Furthermore, the alterations in catalase, glutathione peroxidase, and glutathione-S-transferase activities in the pancreas of santalinpretreated rats could be responsible for preventing damage to the pancreas and thus non-induction of diabetes following alloxan treatment. Therefore, for the first time, we report the simplified procedure for isolating a mixture of santalins, including their ability to prevent the induction of diabetes in Wistar rats. The outcome of our study has significant clinical importance to the fact that supplementation of santalins may potentially avoid or delay the onset of diabetes in high-risk individuals.

Possible Short-Term Biological Effects of Kefir Beverage: Ⅰ: Effect of Kefir Beverage on The Cell Biological, Histochemical, Histopathological and Biochemical Changes in Pancreas of High Fat-Fed STZ- Induced Diabetic Male Wistar Rat

The present study was designed to investigate the biological effects of kefir and whether kefir consumption protects and/or repairs the pancreas of high-fat diet-fed streptozotocin-diabetic rats, and how does it do that?. Our results showed Kefir decreased both the volume of nuclei and RNA content and increased both collagen and lipoproteins material contents in the normal pancreatic cells. Also, kefir increased RNA, protein, and lipoproteins materials content and decreased the volume of nuclei of pancreatic cells in diabetic male rats. Immunohistochemically, kefir showed highly immunoreactive signals of insulin granules inside the Langerhans Islands. Our results showed kefir consumption had a beneficial effect on controlling the glycemic state in diabetic rats by lowering insulin levels and kept the pancreas tissue structurally almost normal. Kefir probably acts as follows: From the cell biological and histochemical points of view, the results showed an increase in the nuclei volume and DNA, RNA, and total protein contents in the pancreatic cells of diabetic rats treated with kefir. Also, the biochemical and immunohistochemical results showed an increase in insulin hormone (functional protein) of these pancreatic cells, which’s probably a result of an increase in the cellular activities or/and the number of beta cells. Finally, therefore we propose that kefir has a stimulatory effect on the cellular activity of beta cells leading to activation of genes responsible for the protein synthesis included insulin hormone, and/or increasing the cell proliferation of beta cells in the pancreas of diabetic rats. From Cell biological, Histochemical, Immunohistochemical, pathological, and Biochemical points of view, the preclinical treatment with kefir or insulin of normal or diabetic male rats, beneficially highly alternates the cellular activities, histochemical and immunohistochemical materials components, and histological architecture. of the pancreas therefore Kefir and insulin may, to some extent, repair the pathological side effects of type 1 diabetes mellitus. The positive results of using kefir and insulin in treating the Pathogen effects of type 1 diabetes mellitus on the pancreas of male mice gave us a hope of possibility to obtain positive clinical applications/implications. Therefore, these positive beneficial results make us continue our work and complete the various pre-clinical trial and clinical experiments phases.

Effect of black pepper, turmeric and ajwa date on the endocrine pancreas of the experimentally induced diabetes in wister albino rats: A histological and immunohistochemical study

BackgroundDiabetes is now a global problem and millions of people are suffering all over the world. Reports exist for the allopathic use of turmeric, black pepper, and date palm as an antidiabetic and antioxidant agent. AimThe current study was designed to assess the antihyperglycemic, antioxidants and antihyperlipidemic consequences of black pepper (BP), turmeric (T), ajwa pulp (AP), and ajwa seeds (AS) in alloxan-induced diabetic rats. MethodologyDiabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in rats. They were randomly divided into 11 groups of 18 male and 18 female rats each. Group-1 normal control, group-2 diabetic control, group-3 was administered with glibenclamide (10 mg/kg), group-4 was administered with aqueous extract of BP (50 mg/kg), group-5, 6, 7 were administered with T, AP and AS (500 mg/kg) and group-8, 9, 10, 11 were administered with different combinations of aqueous extract (500 mg/kg) once in a day for eight weeks. The antihyperglycemic potential was determined through biochemical and histological investigations of the experimental animals at the end of the experiment. ResultsThe results of the study revealed that treatments improved glucose (229.53 mg/dL), Ghb (7.68%), insulin (13.63 U/L), Tg (95.92 mg/dL), Tc (152.86 mg/dL), HDL (23.22 mg/dL), LDL (110.30 mg/dL), TAC (1.89 mmol/L) and TOS (20.05 μmol/L) in comparison to diabetic control rats after 8 weeks of study period. Histological and immunohistochemical investigation of tissues exhibited severe changes in the pancreas of diabetic rats and treatments modulate these changes; this improvement in cells may explain the antidiabetic effects. ConclusionIt is concluded that aqueous extract of BP+AS; and BP+T+AP+AS could be promising nutraceutical therapy for diabetes management and its associated complications.

Histopathological effects of zinc oxide nanoparticles prepared by Vaccinium arctostaphylos ethanolic fruit extract on liver and pancreas of diabetic rats

Histopathological effects of zinc oxide nanoparticles prepared by Vaccinium arctostaphylos ethanolic fruit extract on liver and pancreas of diabetic rats

Acute Toxicological and Histopathological Elucidation of Rheum emodi Rhizome Extract to Demonstrate Antidiabetic Activity in Alloxan-induced Diabetic Rats

Background: Rheum emodi has been used traditionally to treat diabetes in India. The study was designed to elucidate the effect of 75% ethanolic extract of R. emodi (rhizome) (EE-ReR) and its isolated compounds like emodin and chrysophanol on alloxan-induced diabetic rats, and to check its antidiabetic efficacy. Acute toxicological and histopathological studies were also assessed. Methods: Experimental rats were divided into six groups, with each group consisting of 6 rats. EEReR and its compounds emodin and chrysophanol were given orally for 30 days. Results: The experimental rats were sacrificed after 30 days by cervical dislocation. The renal profile and lipid parameters were determined. Histopathological changes in liver, kidney and pancreas were examined in EE-ReR treated group. EE-ReR was fed orally to diabetic rats, which resulted in a decline in the fasting blood glucose, total cholesterol, free fatty acids, creatinine, urea levels, and a rise in the insulin levels was observed almost in the normal range, in the rats which were fed with the extract. Histopathological studies of pancreas, kidney, and liver in diabetic rats revealed that the treated group of rats showed normal regeneration of islets cells. Acute toxicological studies revealed that the extract is safe up to 2000 mg/kg body weight of extract fed orally. Conclusion: These findings are suggestive of a possible protective and prevent damage to the internal organs played by the R. emodi and its compounds like emodin and chrysophanol compounds and elevate insulin production during high blood glucose levels without any acute toxicologically effect.

Antidiabetic and antihyperlipidemic activities of a novel polyherbal formulation in streptozotocin - nicotinamide induced diabetic wistar rats

Objective: To investigate the antidiabetic and antihyperlipidemic activities of polyherbal formulation (PHF) containing seven plants namely Cassia auriculata, Cassia fistula, Syzygium cumini, Cyperus rotundus, Saussurea lappa, Terminalia arjuna and Salacia reticulate in streptozotocin (STZ) - nicotinamide (NC) induced diabetic rats by administering oral doses (200 and 400 mg/kg body weight).
 Materials and Methods: Animals were divided into diabetic and nondiabetic groups. Rats were fed with normal laboratory diet and induced with a single intraperitoneal injection of 60mg/kg of STZ, and thereafter 120 mg/kg NC was injected after 15min. Diabetic rats were treated with formulation (200 and 400 mg/kg) and glibenclamide 5 mg/kg. Blood glucose levels were measured using blood glucose test strips with ACCU CHEK glucometer. Glycosylated haemoglobin, total haemoglobin, lipid profiles, lipoproteins, hepatic marker enzymes activity were determined in normal and STZ- NC induced diabetic rats after oral administration of the PHF for 28 days. Histopathological changes in normal and diabetic rat pancreas organs were also observed after PHF treatment.The statistical analysis of results was carried out using one-way analysis (ANOVA) followed by post hoc multiple comparison tests.
 Results: Treatment of diabetic rats with PHF (200 and 400 mg/kg) and glibenclamide (5 mg/kg) indicate significant decreased blood glucose level and significant improvement in body weight. PHF treated rats showed significant (P < 0.01) decrease in the level of HbA1C, TC, TG, LDL, VLDL, AST, ALT and ALP while a significant increment in the level of Hb, HDL cholesterol was observed. Furthermore, the PHF treated rats has a favourable effect on the histopathological changes of the pancreas in STZ-NC induced diabetes.
 Conclusion: These findings suggested the antihyperglycemic and antihyperlipidemic properties of the PHF and thus help in preventing future complications of diabetes.

Exenatide promotes cholesterol efflux in pancreatic tissue of obese diabetic rats

To study the effect of exenatide on the expression of ABCA1 and cholesterol metabolism in the pancreas of obese diabetic rats. Twenty-four normal male SD rats and 18 obese diabetic rats (induced by high-fat feeding and STZ injection) were both divided equally into 2 groups for injections of saline or exenatide. After treatment for a week, the expression of ABCA1, cholesterol metabolism, and islet function of the rats were examined using real-time PCR, Western blotting, oil red O staining, cholesterol content determination, and HE staining. The expressions of ABCA1 at both mRNA and protein levels in pancreatic tissue were significantly lower in obese diabetic rats than in normal SD rats. The obese diabetic rats showed obvious lipid deposition and increased cholesterol content in the pancreatic tissue with significantly reduced islet volume and structural changes (P < 0.05); exenatide treatment of the diabetic rats significantly up-regulated ABCA1 expression, reduced lipid deposition and cholesterol content in pancreatic tissue, and increased number and volume of the islets, which presented with more orderly alignment (P < 0.05). Obese diabetic rats have lowered ABCA1 expression, cholesterol efflux block, and cholesterol accumulation in the pancreatic tissue. Exenatide can up-regulate ABCA1 expression and promote cholesterol efflux to reduce cholesterol content in the pancreatic tissue and improve islet function in obese diabetic rats.

Antioxidant and Antidiabetic Effect of Capparis decidua Edgew (Forssk.) Extract on Liver and Pancreas of Streptozotocin-Induced Diabetic Rats

Introduction: The twig of Capparis decidua has been traditionally used as an antidiabetic agent but its medicinal use has not been scientifically proved yet. Present study evaluated the antidiabetic effect and antioxidant activities of aquatic extract of twigof Capparis decidua on liver and pancreas of diabetic rats induced by Streptozotocin (STZ). Materials and Methods: The effect of Capparis decidua was evaluated by biochemical, histological and FTIR studies. All biochemical and biophysical parameters were estimated after 15 days of daily oral administrations of the aqueous extract. Results: Results showed that oral use of Capparis decidua extract (250 mg/kg) caused significant reduction in the fasting blood glucose levels in diabetic rats when compared to control rats. Moreover, the altered level of lipid peroxidation, antioxidant, lipid profiles, liver enzymes, and also structural changes were reversed in STZ-induced diabetic rats which received Capparis decidua extract. Conclusions: In conclusion, aqueous extract of Capparis decidua has potent antidiabetic and antioxidant activity.

Hypoglycemic effect of low-sugar juice derived from Hovenia dulcis on type 1 diabetes mellitus rats.

Fruit juice is usually rich in monosaccharides and disaccharides. A reverse osmosis separation machine was used to remove monosaccharides and disaccharides from Hovenia dulcis fruit juice, leaving behind most of the bioactive substances in a low-sugar fruit juice (LSFJ), so as to provide a more effective treatment for diabetic patients. This study was carried out with type1 diabetes mellitus model induced with high dose of streptozotocin (60 mg kg-1 ), and oral administration of LSFJ for 4 weeks. LSFJ treatment led to significant gain in body weight and increased serum insulin level, insulin-like growth factor-1 level, blood urea nitrogen level, creatinine level, and hepatic glycogen level. Meanwhile, fasting blood glucose, fructosamine level, and glucose tolerance were also observably enhanced. Additional, LSFJ treatment significantly improved lipid metabolism, islet quality, and islet oxidative stress. The messenger RNA levels of glucose metabolism genes in the pancreas of diabetic rats decreased in the diabetes model group, whereas messenger RNA expression of these genes was significantly increased with LSFJ treatment. These findings indicate that LSFJ can improve symptoms associated with type 1 diabetes mellitus. The research also suggests new strategies for diabetes prevention and treatment. © 2021 Society of Chemical Industry.

Antidiabetic effects of curcumin/zinc oxide nanocomposite in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is a tremendously widespread endocrine disease that causes many complications risking patient’s quality of life. The current study aims to evaluate the antidiabetic potential of curcumin nanoparticles (Curc-NPs), Zinc Oxide nanoparticles (ZnO-NPs), and Curcumin/Zinc oxide nanocomposite (Curc/ZnO-NC) on streptozotocin (STZ)-induced diabetic rats. Results are compared to rats treated by traditional anti-diabetic Diamicron and to normal non-diabetic rats. Adult Wistar albino rats with weight (180-200 g) were divided into 6 groups, each group contains 8 rats (4 males and 4 females). To induce type 2 DM, five groups were injected intraperitoneal with a single dose of 50 mg/kg b.w. freshly prepared STZ. Each group of diabetic rats were treated orally with a daily dose of 50 mg/kg b.w. of Curc-NPs, 10 mg/kg b.w. of both ZnO-NPs & Curc/ZnO-NC, and 5 mg/kg b.w. of Diamicron for 21 days. The antidiabetic potential of every treatment against diabetic rats was evaluated by investigating different biochemical parameters (glucose, insulin, urea, creatinine, HbA1-C, AST, ALT) and histopathological parameters as well as protein expression of Glucokinase (GK) and Glucose transporter protein 2 (GLUT-2) in the pancreas and livers of diabetic rats. All treated groups showed significant reduction in blood glucose, elevated insulin levels, regulated GLUT-2 and GK genes, however, Curc/ZnO-NC showed the most potent anti-diabetic activity compared to normal rats, the histopathological findings correlate with the achieved data.

Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats.

Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10 % fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6-phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.

Protective effects of a standardized extract of Iris germanica on pancreas and liver in streptozotocin-induced diabetic rats.

Background and purpose:Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats.Experimental approach:Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE).Findings/Results:Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level.Conclusion and implication:These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.

Curculigo pilosa mitigates against oxidative stress and structural derangements in pancreas and kidney of streptozotocin-induced diabetic rats.

Background Curculigo pilosa (African crocus) is widely used in folklore medicine to treat diabetes mellitus and its associated complications. This study was carried out to evaluate this traditional claim by mechanistic investigation of the effect of corn steep liquor extract of Curculigo pilosa and its n-butanol and methanol solvent fractions on hyperglycemia mediated oxidative damage in pancreas and kidney of streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced by single intraperitoneal administration of (50 mg/kg) streptozotocin and diabetic rats were treated orally with the extract(s) once in a day for 28 days. After experimental period, the effect of the extract(s) on hyperglycemia mediated oxidative stress was assessed by determination of lipid peroxidation (LPO), reduced glutathione (GSH), nitric oxide (NO), hydrogen peroxide (H2O2) and activities of catalase (CAT) and superoxide dismutase (SOD) enzymes. Also histopathology studies were conducted to substantiate the protective effects on pancreas and kidney. Results Oral administration of the extract significantly (p<0.05) mitigated the hyperglycemia mediated oxidative damage via improving the antioxidant system, inhibit the generation of lipid peroxide, hydrogen peroxide and nitric oxide. Also administration of extracts improved the structural architecture of the pancreas and kidney tissues in diabetic rats. Conclusion The results obtained in this study provide resounding scientific support for the folkloric use of Curculigo pilosa in the management of diabetes mellitus and its complications.

Launaea acanthodes (Boiss) O. Kuntze mediates hepatic glucose metabolism and ameliorates impaired pancreatic function in streptozotocin-induced diabetic rats

Ethnopharmacological relevanceLaunaea acanthodes (Boiss.) O. Kuntze is native to semiarid regions of central Iran, traditionally used in the treatment of numerous disorders including diabetes. Aim of the studyThe current study aimed to explore hypoglycemic activity of Launaea acanthodes extract in streptozotocin-induced diabetic rats. Furthermore, gene expression study was carried out to examine expression levels of key glucose metabolism-related genes. MethodsFor in vitro study, Folin-Ciocalteus, DPPH and aluminum chloride colorimetric assays were used to determine the total phenolic content, antioxidant capacity and total flavonoid content of extracts, respectively. For in vivo study, streptozotocin-induced diabetic Wistar rats were orally administered with metformin (50 mg/kg) and various doses of extracts (100, 200 and 400 mg/kg body weight) for 28 days. Fasting blood glucose, body weight, food and water intake were assessed during the course of treatment. At the end of the intervention, oral glucose tolerance test (OGTT), lipid profile and glycated hemoglobin (HbA1c) were evaluated. Furthermore, functional liver enzymes, oxidative stress markers and histopathology of pancreas were examined. Lastly, quantitative real time polymerase chain reaction (qRT-PCR) was applied to explore the mRNA levels of genes relevant to glucose metabolism in the pancreas and liver tissues of diabetic rats. ResultsBased on the in vitro results, the hydroalcoholic extract revealed potential radical scavenging activity and contained highest amount of phenolic and flavonoid. The in vivo results demonstrated that the extract lowered fasting blood glucose level, increased the body weight, restored the alterations in the levels of water and food intake, attenuated HbA1c, improved lipid profile and ameliorated the OGTT in diabetic rats. The extract administration alleviated the histopathological changes in the pancreas, suppressed malondialdehyde (MDA) level and further restored attenuated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in diabetic rats. Analysis of real time PCR data showed that extract administration reversed the expression levels of hepatic glucokinase (GK), phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, the extract upregulated the expression level of glucose transporter-2 (GLUT-2) and pancreatic-duodenal homeobox (PDX-1) in diabetic rats. ConclusionCollectively, the results demonstrate that Launaea acanthodes hydroalcoholic extract exerts hypoglycemic effect possibly via regulating key enzymes of glucose metabolism and ameliorating pancreatic dysfunction through its antioxidant properties.

Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Cotula cinerea (Del) in Normal and Streptozotocin-Induced Diabetic Rats.

The current investigation aimed to assess the antioxidant, antidiabetic and antilipidemic effects of the aqueous extract of aerial part of Cotula cinerea (C. cinerea). Cotula cinerea (Del). which belongs to the Asteraceae family is commonly used traditionally for the treatment of diabetes. The objective of the study was to study the effect of the aqueous C. cinerea extract on glucose and lipid metabolism in normal and streptozotocin-induced diabetic rats using a single and repeated oral administration. A preliminary phytochemical screening and the quantification of phenolic and flavonoid contents as well as the antioxidant activity using three methods (DPPH, FRAP and ABTS) were carried out. The effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of aerial part of Cotula cinerea (AEAPCC) at a dose of 20 mg/kg on glucose and lipid profile was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of the pancreas and liver was carried out according to the Hematoxylin-Eosin method. AEAPCC (20 mg/kg) showed a significant blood glucose-lowering activity in both normal and diabetic rats after a single and repeated oral administration during 15 days. The aqueous extract was also able to decrease the plasma triglycerides levels in both normal and diabetic rats after 15 days of oral treatment at a dose of 20 mg/Kg while no effect was observed on plasma cholesterol levels. In addition, the results show that AEAPCC exhibits an in vitro antioxidant activity using different tests. Histopathological analysis of the pancreas and liver of AEAPCC-treated diabetic rats has revealed that AEAPCC had a beneficial effect on the architecture of these organs while no improvement of glucose tolerance was noticed using the glucose tolerance test. Furthermore, the results showed that the extract is rich in several phytochemical compounds and exhibited an important antioxidant activity. The phytochemical screening revealed that AEAPCC contains polyphenolic compounds, flavonoids, tannins, alkaloids, saponins, quinones, sterols, terpenoids, anthroquinones and reducing sugars. Whereas, it is free from glycosides. In conclusion, this study demonstrates that Cotula cinerea possesses a beneficial effect on diabetes. Further investigations are required to study the mechanism of action of the antidiabetic effect of this plant.

Semi-modified okara whey diet increased insulin secretion in diabetic rats fed a basal or high fat diet.

Lifestyle and diet preferences are primarily responsible for developing type 2 diabetes. In this study, okara was manufactured into okara whey crackers (OWC) to investigate its dietary role in controlling diabetes in streptozotocin-diabetic rats with and without a high-fat diet. Forty-eight rats were divided into eight groups. G1-G4 were nondiabetic and fed a basal diet, a basal diet with 30% crackers, high fat diet, and a high-fat diet with 30% crackers, respectively. G5-G8 were diabetic groups that received similar diets as previous groups. Blood glucose, liver function, lipid pattern, pancreas and liver histopathology, and insulin immunohistochemistry were performed. OWC improved measured parameters and histopathology of the liver and pancreas in diabetic rats. The area % of positive insulin cells was increased in G6 (5.20%) and G8 rats (2.83%) fed OWC compared to diabetic rats (1.17%). In conclusion, the use of 30% OWC in a semi-modified diet has controlled the hyperglycemia and hyperlipidemia associated with diabetes.