Pancreas Of Diabetic Rats Research Articles

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 < 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.

Histological and Biochemical Alterations in the Pancreas of Diabetic Wistar Rats Treated with Garcinia Kola and Tetracarpidium Conophorum Extracts

To ascertain the stated effects, phytochemical and LD 50 studies of the extracts were determined. Thirty-six adult male Albino Wistar rats weighing 180 – 200 g were divided into 6 groups (n =6). Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (45 mg/kg bw) reconstituted in citrate buffer pH 4.5, and rats with fasting blood glucose (FBG) ≥ 11.3 mmol/L after three days of induction were used for the study. Glibenclamide significantly (p < 0.05) reduced FBG from 22.10 ± 1.65 mmol/L to 4.48 ± 0.29 mmol/L, G. kola from 22.04 ± 4.06 mmol/L to 7.40 ± 2.41 mmol/L, T. conophorum from 14.26 ± 2.38 mmol/L to 5.98 ± 0.57 mmol/L, and combined from 17.54 ± 1.72 mmol/L to 11.58 ± 2.11 mmol/L. Glibenclamide and the extracts significantly increase the insulin levels. G. kola significantly (p < 0.05) lowered the urea and raised the chloride and creatinine levels. T. conophorum significantly (p < 0.05) reduced the urea and increased the sodium and chloride levels, while the combined treatment significantly lowered the urea and raised the sodium levels. Glibenclamide and the extracts significantly ameliorated the histological alterations in the pancreas but only the plant extracts significantly attenuated the alterations in the kidneys. It may be concluded that the combined administration of G. kola and T. conophorum extracts and their single treatments showed hypoglycaemic and nephroprotective effects. Keywords: Albino Wistar rats, Streptozotocin, Glibenclamide, Garcinia Kola, Tetracarpidium conophorum, Pancreas, Kidney DOI: 10.7176/JNSR/13-14-04 Publication date: July 31 st 2022

Ameliorating Effect of Malva neglecta Wallr on Obesity and Diabetes in Wistar Rats: A Mechanistic Study.

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 − 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 − 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds.

Comparing and Optimizing RNA Extraction from the Pancreas of Diabetic and Healthy Rats for Gene Expression Analyses.

Advanced differential gene expression analysis requires high-quality RNA. However, isolating intact pancreatic RNA is challenging due to abundant pancreatic ribonucleases, which limits efficient downstream gene expression analysis. RNAlater treatment reduces endogenous ribonucleases effects through either pre-organ excision via organ mass or bile duct direct injection or organ mass injection post-isolation. We compared RNA extraction protocols to establish a reproducible and effective pancreatic RNA extraction method to obtain high RNA integrity number (RIN) values from healthy and streptozotocin (STZ)-induced diabetic rats for gene expression analyses. Different methods were tested focusing on RNase activity inhibition using RNAlater (Qiagen) pre-harvest of the pancreatic tissue, and extracted RNA quality and concentration were analyzed using NanoDrop spectrophotometer, Agilent Bioanalyzer, and RT-PCR. Inclusion of several pre- and post-excision modifications in the RNeasy Mini Kit (Qiagen) protocol resulted in RIN values more than two-fold higher compared to those using the standard protocol. Additionally, RT-PCR amplification of the housekeeping gene, β-actin, revealed no differences in extracted RNA quality from healthy and STZ-induced diabetic rats. We compared and developed a more effective and reproducible pancreatic RNA extraction method from healthy and diabetic rats, which resulted in RNA of superior quality and integrity and is suitable for complex molecular investigations.

Spexin Co‐localizes with Insulin in Pancreatic Islet Cells of Normal and Diabetic Rats

Spexin is a newly discovered gastrointestinal tract (GIT) peptide. Preliminary biochemical analysis showed that spexin was localized to secretory granules in a transfected pancreatic cell line. Spexin was also expressed in the submucosal cells of the mouse stomach indicating that it is a resident peptide in the GIT and may thus influence pancreatic function. It has been suggested that spexin may play a role in the regulation of physiological homeostasis. Our aim was to determine whether spexin is present in the pancreas of normal and streptozotocin‐induced diabetic rats. We also wanted to know whether spexin co‐localizes with pancreatic hormones in the islet of Langerhans. Immunohistochemical, immunofluorescence and transmission electron microscopy (TEM) methods were used to determine the cellular localization of spexin in the endocrine pancreas of non‐diabetic and diabetic rats. Immunofluorescence study showed that a significant number of cells in the core of rat pancreatic islet contains spexin, where insulin‐positive cells are located. We used double labelling immunofluorescence method to determine whether spexin and insulin co‐localize together in the same cell. We observed that these spexin‐immunoreactive cells also contain insulin. There was no evidence of co‐localization of spexin with either somatostatin or pancreatic polypeptide. The number of spexin‐ and insulin‐immunopositive cells was significantly (p &lt;0.05) reduced after the onset of diabetes mellitus. Moreover, TEM showed that the secretory granules of pancreatic beta cells contain spexin‐labelled immunogold particles. In conclusion, the presence of spexin in pancreatic beta cells suggests a role in the regulation of pancreatic endocrine function.

Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas.

Nitric oxide is generated from nitric oxide synthase following hyperglycemia-induced oxidative stress during the course of diabetes mellitus (DM). We examined the temporal immuno-expression of neuronal nitric oxide synthase (nNOS) in the pancreas of diabetic and non-diabetic rats using immunohistochemical, immunofluorescence and western blot techniques 12 h, 24 h, 1 week, 2 weeks, 1, 8 and 15 months after induction of DM. nNOS co-localized with pancreatic beta cells but disappears 12 h after the onset of DM. In contrast, the nNOS content of pancreatic nerves increased significantly (p < 0.001) 24 h after the induction of DM, and decreased sharply thereafter. However, nNOS-positive ganglion cells were observed even 15 months post-diabetes. ROS increased by more than 100% two months after the onset of DM compared to non-diabetic control but was significantly (p < 0.000001) reduced at 9 months after the induction of DM. The pancreatic content of GSH increased significantly (p < 0.02) after 9 months of DM. Although, TBARS content was significantly (p < 0.009; p < 0.002) lower in aged (9 months) non-diabetic and DM rats, TBARS rate was markedly (p < 0.02) higher 9 months after the induction of DM when compared to younger age group. In conclusion, nNOS is present in pancreatic beta cell, but disappears 12 h after the onset of diabetes. In contrast, the tissue level of nNOS of pancreatic nerves increased in the first week of diabetes, followed by a sharp reduction. nNOS may play important roles in the metabolism of pancreatic beta cell.

Comparative Assessment of Portulaca oleracea, Omega-3 Fatty Acids, and Combination of Selenium Plus Vitamin E on Histopathology of Pancreas in Diabetic Rats

Introduction: Antidiabetic effects of Portulaca oleracea (PO) plant, omega-3 and a combination of Selenium and Vitamin E have been reported which could compensate for defective insulin release and enhance antioxidant levels. The purpose of the present study was to compare the serum glucose levels and histopathological effects on PO, Omega-3, and a combination of Selenium and Vitamin E in the pancreas of adult male diabetic rats.&#x0D; Materials and methods: A total of 96 adult male Wistar rats, weighing approximately 220 g were used. The rats were divided into four groups with 4 replicates for each group accidentally. The rats were diabetic via a single injection of streptozotocin solution (60 mg/kg, IP injection). The groups contained the control group of diabetic rats, which received the standard ration daily, the second group of diabetic rats was fed the standard ration plus Portulaca oleracea extract (1.5 mg/kg/day/orally), the third group of diabetic rats was fed standard ration plus omega 3 (500 mg/kg/day/orally), the fourth group of diabetic rats was fed standard ration plus Vitamin E (400 iu/kg/day/orally) and Selenium (0.5 mg/kg/day/orally) for a period of 14 days. At the end of the study, the samples were taken for histopathological investigation of the pancreas and serum glucose levels. The mean diameter of pancreatic islets and percentage of beta and alpha cells were calculated in all groups.&#x0D; Results: The percentage of alpha cells in the treatment groups was higher than in the control group. The percentage of beta cells in the third group was higher than in the fourth group and control group. The mean diameter of pancreatic islets in omega-3-treated rats was higher than in other groups. The insulin level increased in treated rats in comparison with the rats that were not treated significantly.&#x0D; Conclusion: Diabetic male rats treated with omega-3 showed more positive effects on pancreatic islets and blood glucose compared to other treatment groups.

Effects of Moringa oliefera Lam. Aqueous Root Extract on the Histology of Pancreas in Alloxan-Induced Diabetic Rats

This study was to determine the effects of aqueous root extract of Moringa oleifera on antioxidant activities and on the histology of pancreas in Alloxan-induced-diabetic rats. Twenty Albino Wistar rats of both sexes weighing between100 and 194g were used for the study. The animals were divided in to four groups (Groups I, II, II and IV) of five rats each. Group I was the control group and were administered distilled water per body weight. Group II was induced with diabetes by injecting the rats with 150mg/kg Alloxan single dose and not treated. group III was induced with diabetes and treated with 50mg/kg Moringa for 28 days and group IV were not induced with diabetes but were treated with the aqueous extract of Moringa oleifera root for a period of twenty-eight days at 50mg/kg orally. The antioxidant activity of Moringa oliefera aqueous root extract was studied by assaying serum marker substances of Catalase, Glutathione peroxidase (GPx), Superoxide Dismutase (SOD) and Malondialdehyde (MDA) to determine the extent of antioxidant activity of the extract on the pancreas. At the end of the experiment, the animals were sacrificed and the Pancreas processed for routing light microscopic analyses. The results of this study showed that antioxidant activities of Malondialdehyde (MDA) decreased significantly in diabetic not treated and diabetic treated Moringa groups and Glutathione peroxidase (GPx), activity increased significantly in diabetic non-treated group and non-diabetic treated group (p&lt;0.05). Glutathione Superoxide Dismutase (SOD) and Catalase changes were not significant. The results of this study also showed that photomicrograph of pancreas of diabetic non treated rats showed highly lobulated pancreatic tissue, glands exhibits loose collagenous capsule which can be seen extending as delicate septae, chronic inflammation and degeneration of islets of Langerhans. Diabetic treated group also showed septea between the lobule similar to the control group and glandular acini undergoing regeneration. Non-diabetic but treated group showed diffused micro and macro acini and normal islets of Langerhans similar to control.

Effects of Creatine Supplementation on Histopathological and Biochemical Parameters in the Kidney and Pancreas of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.

Effect of Cymbopogon citratus (Lemon grass) on the Expression of Insulin sensitive and Proinflammatory Genes in the Pancreas of Diabetic Rats

Inflammation may result from chronic hyperglycemia, a disease of macromolecule metabolism disorder caused by diabetes mellitus due to insulin malfunction. Although Cymbopogon citratus (Lemon grass) has long been used as an anti-diabetic, not much is known about the mechanisms involved. The goal of this study was to see how C. citratus leaf extract modulates genes related to insulin sensitivity and inflammation in alloxan-induced diabetic rats' pancreas. Control, diabetic control, metformin (100 mg/kg), and C. citratus (100, 200, and 400 mg/kg) were the six groups of experimental rats. Alloxan (150 mg/kg) was administered intraperitoneally to five groups. ACCU-CHEK glucometer and glucose test strips were used to measure fasting blood glucose at three-day intervals. Treatments were given for fourteen (14) days after which the animals were sacrificed and the pancreas removed for RT-PCR analysis. Image J software and graph pad prism software were respectively used to quantify and present the results. Diabetes induction by alloxan significantly (p&gt;0.05) increased fasting blood glucose level compared to non-induced control after 3 days. Administration of C. citratus aqueous extract (14 days) reduced the blood glucose of diabetic rats significantly (p&lt;0.05). C. citratus up-regulated the expression of TGR5, PPAR-γ, GLUT2, and Glucokinase genes relative to diabetic control respectively. It also down-regulated IL-6 and TNF-α genes expression relative to diabetic control rats. The antidiabetic effect of C. citratus could be via its ability to up-regulate the expression of genes associated with insulin sensitivity and down-regulate the expression of pro-inflammatory genes.

Effect of Kombucha and Its Non-Polar Components on Morphological Aspects of the Pancreas of Diabetic Rats with Streptozotocin

Objective: to evaluate the protective effect of kombucha and its components not polar, in pancreas of diabetic rats treated with streptozotocin. Material and methods: ninety-six male Wistar rats of 120 to 170 g of PC were used; four groups of 24 animals were formed: control (GC), control treatment (GCTx), kombucha treatment (GTxK) and treatment with non-polar components of kombucha (GTxCNP). Diabetes was induced in the last three groups with an intraperitoneal injection of streptozotocin at a dose of 65 mg/kg BW. At the same time, treatment was started in the different groups; GC and GCTx groups were administered, orally, 1 ml of sterile saline solution; to the GTxK group 324 mg/kg of kombucha; and to GTxCNP 0.006 mg/kg of the non-polar components. For the histopathological study, pancreas samples were obtained on days 1, 7, 14 and 21 and fixed in formalin. They were processed with the histological technique, 5-micron-thick sections were made and stained with the hematoxylin-eosin technique. Finally, the number of islets of Langerhans per field observed with the 10x objective was quantified. The results were subjected to a one-way analysis of variance and Tukey’s test (p β cells of the pancreas and the Islets of Langerhans. Specific additional studies on the main, non-polar components of kombucha are suggested to know the mechanism of protection on pancreatic islets.

Evaluation of Antidiabetic Activity of Vitis pedata in Alloxan Induced Diabetic Rats

The primary focus of the research was to evaluate the antidiabetic activity of the ethanolic and aqueous extract of Vitis pedata in alloxan induced rats. The entire study was divided into two phases: Phase 1 and phase 2. The phase 1 is initiated with the collection and authentication of the plant, followed by extraction with ethanol and water and finally screening of the phytochemical constituents of the extracts. The phase 2 is more inclined on the therapeutic effect of the plant extracts on experimentally induced diabetic rats. Several parameters such as estimating the body weight and liver weight, blood glucose level, total proteins, hemoglobin, serum albumin, serum urea, serum cholesterol levels were examined in the diabetic rats. The histopathological changes in the pancreas of diabetic rats were also studied. The aqueous extract of Vitis pedata showed a significant reduction in the blood glucose levels, lipid profile and serum biomarkers in diabetic rats, quite similar to the standard treatment of glibenclamide, whereas the ether extract showed a less effect compared to the other two extracts. The plant extracts also highlighted an improvement in the beta cell mass in islets of pancreas. Thus, the study of aqueous and ethanolic extract of Vitis pedata indicated a promising antihyperglycemic activity in alloxan induced diabetic rats. Furthermore, the study also opens the door for extended research to explicate the mechanism of action of the plant extracts.

HEPATOPROTECTIVE AND HISTOLOGICAL PANCREAS EFFECTS OF Sarang Banua (Clerodenrum fragrans Vent Willd) LEAF EXTRACT IN ALLOXAN-INDUCED DIABETIC RATS

Research on anti-diabetic herbal plants and their safety continues to grow by the increasing number of diabetics, especially in Indonesia, which is rich in plant biodiversity. This study investigated the effect of Sarang banua (Clerodendrum fragrans Vent Willd) leaf extract on the hepatoprotective effect, histology of the pancreas, and serum glucose levels of white male rats (Rattus novergicus) induced diabetes by alloxan. Diabetic rats were given ethanol extract of C. fragrans leaf (100, 200, and 300 mg/kg bw), ethyl acetate extract (200, 300 mg/kg bw), and metformin (125 mg/kg) orally for 14 days. Enzym activities and glucose levels in serum were determined at the end of treatments. The histology of rat pancreas and liver were observed under an electron microscope with 10x magnification. The data obtained were analyzed by ANOVA followed by the Least Significant Difference test. The results showed that the administration of ethanolic extract of C. fragrans leaves at 100mg/kg bw significantly decreased the serum glutamicoxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and serum glucose levels in the alloxan-induced diabetic rat (p &lt; 0.05). C. fragrans leaf extract decreased the level of histological damage liver and pancreas of alloxan-induced diabetic rats. The C. fragrans improved the protective effects on the liver, and pancreas, and decreased serum glucose in alloxan-induced diabetic rats.

The protective effects of vitamin D3 on histopathology of pancreas and liver in streptozotocin-induced diabetic rats

The protective effects of vitamin D3 on histopathology of pancreas and liver in streptozotocin-induced diabetic rats

Modulation of Notch signaling and angiogenesis via an isolated polysaccharide from Momordica charantia in diabetic rats.

Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of the isolated polysaccharide from Momordica charantia in diabetic rats. The polysaccharide was isolated from M. charantia (MCP) and was characterized by using FTIR and LC-MS/MS. The diabetic model was established by intraperitoneal administration of streptozotocin in male Wistar rats and grouped into control, diabetic, metformin (500mgkg-1 day-1 ), and treatment (10mgkg-1 day-1 ) groups. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31, and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the polysaccharide structure of the isolated fraction. High blood glucose was normalized by MCP treatment in diabetic rats. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1, and Hes1 while it scaled down the levels of Notch1, Dll4, and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining levels of hes1, cyclin d1, and VEGF proteins were increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets' regeneration and suggest that modulation of notch and angiogenesis pathways may play a pivotal role in the restoration of the islets to relieve diabetes. PRACTICAL APPLICATIONS: Polysaccharides extracted from Momordica charantia could normalize the level of blood glucose in STZ-induced type 2 diabetic rats through modulation of notch and angiogenesis singling pathways. Given that this effect was associated with the increased expression of Pdx-1 and Insulin in the pancreas, the isolated polysaccharide is expected to be introduced as a convenient medicine in the treatment of diabetes through modulation of β-cell regeneration.

Palm leaf catechins improved insulin-related pathways in diabetic rats

Catechin-rich oil-palm leaf extract (OPLE) (Elaeis guineensis) was previously demonstrated to possess benefits for diabetes and cardio metabolic health (vasodilation, antioxidant, cardiovascular, anti-hypertensive, anti-inflammatory, hepatoprotective and nephroprotective properties) in animal models. For insights into OPLE anti-diabetic mode-of-action and possible toxicity, the effects of dietary OPLE on insulin-signaling pathways mRNA expressions in the liver, kidney, pancreas, and spleen of normal and diabetic rats were examined. Type-2-Diabetes Mellitus (T2DM) were induced by chronic high-fat diet and streptozotocin (35 mg/kg) intraperitoneal injection. The OPLE (100 mg/kg body weight) were fed daily to normal and T2DM-induced rats. The OPLE suppressed hyperglycaemia and excessive weight gain in the T2DM rats, and appeared harmless to normal rats. The OPLE supplementation significantly (p&lt;0.05) modulated the mRNA expressions of phosphatidylinositol-3 kinase (PIK3R1); insulin signaling receptor (INSR); insulin-receptor substrates 1 and 2; and ectonucleotide pyrophosphatase-1 (ENPP1) especially in the livers of normal rats and the spleen of diabetic rats. Results suggested the OPLE probably help prevent diabetes in healthy mammals and ameliorate the immune functions of diabetic mammals. The OPLE improved the antioxidant defence responses, insulin-pathways mRNA expressions in the normal and diabetic rats; suppressed hyperglycaemia and excessive weight gain in T2DM rodents without observable liver or kidney toxicity at the dose used.

Bee venom attenuates degenerative effects of diabetes associated with hyperlipidemia in rats.

: Natural products have been known as one of the most important therapeutic agents for diabetes and hyperlipidemia. Bee venom is a multipurpose agent that contains different bioactive compounds including melittin and phospholipase A2. Aim: The aim of this study was to investigate the effects of bee venom on biochemical and histopathological abnormalities in pancreas, liver and kidney of diabetic hyperlipidemic rats compared to synthetic drugs (Metformin and Atorvastatin).Material and methods: Bee venom's median lethal dose (LD50) was determined, and then 50 adult male albino rats were divided into five groups: group 1 was fed standard diet and served as a negative control group, while the other four groups were received streptozotocin and nicotinamide injections to induce type 2 diabetes and after diabetes confirmation, rats were fed a high-fat diet for 28 days and then they were divided as follows: group 2 : served as a positive control group, and the remaining three groups represented the treated groups, group 3: bee venom treated group (0.5mg/kg), group

Co-administration of metformin and gallic acid modulates JAK/STAT signaling pathway and glutathione metabolism in fructose-fed streptozotocin diabetic Rats

BackgroundIncidence of diabetes Mellitus (DM) is on the rise with each passing year in spite of available therapies in the management of DM. Metformin, a standard antidiabetic drug, and gallic acid (GA) are some of the compounds with established antidiabetic properties. However, there is dearth of information on their combination on JAK/STAT signaling pathway and glutathione metabolism in diabetic model. This study investigated the combined effect of metformin and GA on diabetic rats. MethodsForty male wistar rats were divided into 5 groups viz: diabetic control, normal control, Metformin (100 mg/kg), GA (100 mg/kg) and GA (100 mg/kg) + Metformin (100 mg/kg). Diabetes was induced by administration of 10% fructose for 14 days followed by injection of streptozotocin (40 mg/kg). The therapy was administered for a total of 21 days. The pancreatic mRNA expression of antioxidant genes (glutamate cysteine ligase catalytic subunits (GCLC), glutamate cysteine ligase modifier subunits (GCLM) and Glutathione Synthetase (GSS), inflammatory genes (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and proteins of the Janus Kinase/ Signal Transducer and Activator of Transcription pathway (Janus Kinase (JAK), Signal Transducer and Activator of Transcription (STAT), were quantified using reverse-transcriptase polymerase chain reaction (RT-PCR). Metformin and GA were also docked with Insulin, GSS, and Janus Kinase 2 (JAK2) to determine their binding affinity. ResultsRats treated with co-administration of GA and metformin significantly (p < 0.05) decreased fasting blood glucose level in comparison with groups treated with gallic acid only and metformin only. The gene expression analysis shows that co-administering metformin and gallic acid protects the pancreas of STZ-induced rats by increasing glutathione production, alleviating inflammation (IL-1, IL-6, IFN-), and modulating the JAK/STAT signaling pathway though upregulation of GCLC, GCLM, GSS mRNA expression and IL-1, IL-6, TNF-α, JAK2, STAT3 and STA5 mRNA expression. ConclusionThis study showed that the combination therapy of metformin and GA modulated JAK/STAT pathway mediated by the cytokines, and replenished glutathione in the pancreas of diabetic rats.

Geraniol ameliorated serum lipid profile and improved antioxidant defense system in pancreas, liver and heart tissues of alloxan-induced diabetic rats

Geraniol ameliorated serum lipid profile and improved antioxidant defense system in pancreas, liver and heart tissues of alloxan-induced diabetic rats

Metformin on Insulin, Glucagon, Oxidative Stress Markers and Pancreatic Tissue Histology in Streptozotocin-Induced Diabetic Rats

This study determined the effects of Metformin on plasma insulin, glucagon, oxidative stress status and histology of pancreas in diabetic rats. Grouping was carried out on 21 rats, and were assigned into 3 groups (n = 7 rats per group); non-DM, DM and DM+metformin (200 mg/kg). Diabetes Mellitus was induced and treatments were given daily by oral gavage for 4 weeks. Food intake, fasting blood glucose (FBG), glucagon, malondialdehyde and protein carbonyl were significantly higher while final body weight, insulin and total antioxidant capacity were significantly lower in Diabetes Mellitus group compared with non- Diabetes Mellitus group. There was significantly higher body weight, insulin level and total antioxidant capacity with significantly lower food intake, FBG, glucagon, malondialdehyde and protein carbonyl levels in Diabetes Mellitus +Metformin group compared with the Diabetes Mellitus group. Pancreatic tissue histology revealed islet cells regeneration in Diabetes Mellitus +Metformin group. This in vivo study provides evidence of the potential of antihyperglycemic and improved oxidants- antioxidant status which may be due to the oral hypoglycaemic nature or effects of metformin as seen in this study.