Diabetic Control Rats Research Articles

P0950EFFECT OF THYROID HORMONE TREATMENT ON RENAL REABSORPTION OF GLUCOSE IN ALLOXAN-INDUCED DIABETIC RATS

Abstract Background and Aims The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Method Adult male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 ?g/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. Results After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Conclusion Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

Effect of Solanum macrocarpon Linn leaf aqueous extract on the brain of an alloxan-induced rat model of diabetes.

ObjectiveThis study was designed to evaluate the protective effect of aqueous extract of Solanum macrocarpon Linn leaf in the brain of an alloxan-induced rat model of diabetes.MethodsThe experimental model of diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan. Rats were then divided into six groups: normal control, diabetes control, diabetes group treated with metformin, and three diabetes groups treated with different concentrations of S. macrocarpon. Rats were sacrificed on day 14 of the experiment and different brain biochemical parameters were assessed and compared between groups.ResultsAdministration of different doses of S. macrocarpon leaf aqueous extract was associated with significantly reduced levels of fasting blood glucose, lipid peroxidation, neurotransmitters, cholinesterases, cyclooxygenase-2 and nitric oxide compared with diabetes control rats. In addition, antioxidant enzyme activities were significantly increased in diabetes rats administered 12.45, 24.9 and 49.8 mg/kg body weight of S. macrocarpon versus diabetes control rats.ConclusionAqueous extract of S. macrocarpon Linn leaf may be useful in the management of diabetic neuropathy.

Auricularia polytricha restores altered reproductive parameters in streptozotocin-induced diabetic Wistar rat

BackgroundLocal Nigerian men use Auricularia polytricha (wood ear mushroom) growing in farm lands and dead woods to manage sexual dysfunction and this practice has been going on for ages without supporting evidence from scientific experiments. This study was to investigate the ameliorative effect of ethanolic extract of Auricularia polytricha on male sex hormones (FSH, LH, and testosterone), sperm parameters (sperm count, sperm motility, and morphology), and histopathological examination of testis using Streptozotocin (STZ)-induced diabetic rats as a model.MethodsThe experiment included five groups of adult male Wistar rat, group A (normal control, treated with normal saline), group B (diabetic control treated with 65 mg/kg.bw of STZ), groups C, D, and E (treated with 250 mg/kg.bw, 500 mg/kg.bw, 1000 mg/kg.bw A. polytricha after inducing diabetics). At termination, homogenate was prepared for semen analysis using improved Neubauer’s hemocytometer, serum samples were used for hormonal assay with ELISA (enzyme-linked immune sorbent assay) kit and light microscope was used for histopathological examination.ResultsResults revealed significant (p < 0.05) reduction in sperm count and motility in group B when compared to normal control, values in group C were not statistically significant (p > 0.05) when compared to diabetic control. However, groups D and E recorded sperm count and sperm motility that were significantly (p < 0.05) increased when compared to the diabetic control (group B). Morphological defects in diabetic control rats were significantly (p < 0.05) higher when compared to normal control but there was no statistical significance in group C when compared to the diabetic control, meanwhile values of sperm morphological defects in groups D and E were significantly (p < 0.05) lower when compared to the diabetic control group. All gonadotropic hormones considered in this research were remarkably lower at p < 0.05 when compared to normal control. However, these values were significantly higher in groups D and E when compared to diabetic control. Structural alterations in cytoarchitecture of testes as a result of sustained hyperglycemia were reversed in a dose dependent manner following A. polytricha administration.ConclusionAlterations in sperm parameters, gonadotropic hormones, and histology of testes caused by diabetes were regulated and reversed following administration of graded doses of A. polytricha. This reversal may be attributed to essential phytochemical and therapeutic constituents in A. polytricha which can be found useful in prevention and treatment of diabetes induced testicular dysfunction.

The effect of endurance training on levels of LINC complex proteins in skeletal muscle fibers of STZ-induced diabetic rats

The changes of the linker of nucleoskeleton and cytoskeleton (LINC) complex have been studied in many muscular abnormality conditions; however, the effects of diabetes and physical activities on it have still remained to be defined. Therefore, the purpose of the this study was to evaluate the impacts of a six-week endurance training on the levels of SUN1 and Nesprin-1 proteins in Soleus and EDL muscles from diabetic wistar rats. A total number of 48 male Wistar rats (10 weeks, 200-250 gr) were randomly divided into healthy control (HC, N = 12), healthy trained (HT, N = 12), diabetic control (DC, N = 12), and diabetic trained (DT, N = 12) groups. Diabetes was also induced by a single intraperitoneally injection of streptozocin (45 mg/kg). The training groups ran a treadmill for five consecutive days within six weeks. The levels of the SUN1 and the Nesprin-1 proteins were further determined via ELISA method. The induction of diabetes had significantly decreased the levels of Nesprin-1 protein in the soleus and EDL muscles but it had no effects on the SUN1 in these muscles. As well, the findings revealed that six weeks of endurance training had significantly increased the levels of Nesprin-1 in DT and HT groups in the soleus as well as the EDL muscles; however, it had no impacts on the SUN1 in these muscles. The muscle fiber cross-sectional area (CSA) and myonuclei also decreased in diabetic control rats in both studied muscles. The training further augmented these parameters in both studied muscles in HT and DT groups. The present study provides new evidence that diabetes changes Nesprin-1 protein levels in skeletal muscle and endurance exercise training can modify it.

Metformin-Mg2+ adjunct therapy synergistically modulates insulin and PDX-1 gene signatures in STZ-NAD induced diabetic model

Diabetes mellitus (DM) is a multi-factorial debilitating disorder of metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia) as a result of defects in either insulin secretion or insulin action in the body. DM is usually accompanied by hypomagnesemia. This study was aimed at investigating the effect of oral magnesium supplementation on pancreatic gene expression of insulin and PDX-1 in type-2 streptozotocin-nicotinamide induced Sprague dawley diabetic rats. A total of 24Sprague dawleyrats (Four groups of six rats each), were used for this study; Group 1: Normal rats (CONTROL) given distilled water for 4weeks; Group 2: Metformin + Magnesium treated rats (DMM) orally given 100mg/kg and 1000mg/kg body weight respectively for 4weeks; Group 3: Metformin treated diabetic rats (DM), orally given 100mg/kg body weight for 4weeks; Group 4: Diabetic untreated control rats (DU) given distilled water for 4weeks. Measured data were analyzed statistically. The result revealed that there was significant (p&lt;0.05) increase in the feed and water intake of the treated rats but the metformin-magnesium supplement treated group showed more increase when compared with only metformin treated group. PDX-1 and insulin gene expression levels were significantly (p&lt;0.05) higher in the control when compared with all the diabetic groups. However, PDX-1 and insulin mRNA levels were significantly (p&lt;0.05) higher in DMM, when compared with DM. DMM showed improvements when compared with DM which suggests magnesium supplementation as an adjunct therapy with metformin may help inthe regeneration of the beta cells of the pancreas.

Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2.

We examined the effect of the NFκB inhibitor pyrrolidine-1-carbodithioic acid (PDTC) on inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) activity, and oxidative and inflammatory kidney damage in alloxan-induced diabetes. Two weeks after diabetes induction (alloxan-130mg/kg), control and diabetic rats received PDTC (100mg/kg) or vehicle for 8weeks. Body weight, glycemia, urea, and creatinine were measured. Kidney changes were measured in hematoxylin/eosin sections and ED1 by immunohistochemistry. Kidney thiobarbituric acid reactive substances (TBARS), superoxide anion (O2-), and nitrate/nitrite (NOx) levels, and catalase and superoxide dismutase (SOD) activities were analyzed. Also, kidney nox4 and iNOS expression, and NFkB nuclear translocation were measured by western blot, and MMP-2 by zymography. Glycemia and urea increased in alloxan rats, which were not modified by PDTC treatment. However, PDTC attenuated kidney structural alterations and macrophage infiltration in diabetic rats. While diabetes increased both TBARS and O2- levels, PDTC treatment reduced TBARS in diabetic and O2- in control kidneys. A decrease in NOx levels was found in diabetic kidneys, which was prevented by PDTC. Diabetes reduced catalase activity, and PDTC increased catalase and SOD activities in both control and diabetic kidneys. PDTC treatment reduced MMP-2 activity and iNOS and p65 NFκB nuclear expression found increased in diabetic kidneys. Our results show that the NFκB inhibitor PDTC reduces renal damage through reduction of Nox4, iNOS, macrophages, and MMP-2 in the alloxan-induced diabetic model. These findings suggest that PDTC inhibits alloxan kidney damage via antioxidative and anti-inflammatory mechanisms.

Effect of Pearl Millet on Glycaemic Control and Lipid Profile in Streptozocin Induced Diabetic Wistar Rat Model

Aims: This study was designed to investigate the effect of Pear millet on glycaemic control and lipid profile in streptozocin diabetic rat model.&#x0D; Methodology: Forty healthy mature male rats were used in this study. The rats divided into 4 groups, ten rats in each and group (A) and (B) normal control rats while group (C) and (D) considered as diabetic rats. Diabetes induced by intraperitoneal injection of 40 mg/kg streptozocin and confirmed by high blood glucose level which considered day 0. The experiment 1, included two groups (A and C), equal rats and the parameters investigated were measured in days 0, 14 and 28. The experiment 2 included two groups (B and D) were received 20% pearl millet and the blood samples were measured in days 0, 14 and 28.&#x0D; Results: The obtained results revealed significant (P&lt;0.05) reduction in insulin and adiponectin (P&lt;0.001) and elevation of blood glucose (P&lt;0.001) in diabetic rats in group C, while significant (P&lt;0.05) reductions in blood glucose, LDL levels and significant (P&lt;0.05) elevation in adiponectin and HDL levels were detected in rats in group B and D. &#x0D; Conclusions: The studies provide evidence that pearl millet induces hypoglycemic effect and improved lipidemic control in diabetic rats.

Modulation of Blood Coagulation and Hematological Parameters by Crassocephalum crepidioides Leaf Methanol Extract and Fractions in STZ-Induced Diabetes in the Rat.

Diabetes affects the homeostasis of the circulatory system. Crassocephalum crepidioides Benth S. Moore (Asteraceae) is an edible plant locally used in the treatment of wounds, stomach ulcer, and skin-related conditions in Africa and some other parts of the world. This study investigated the effects of C. crepidioides leaf methanol extract and fractions on blood coagulation profile of diabetic Wistar rats. The effect of 100 mg/kg body weight of the methanol extract and partitioned fractions of C. crepidioides on blood coagulation profile of STZ-induced diabetic rats were initially evaluated, while graded concentrations (50–200 mg/kg body weight) of the aqueous and hexane fractions were further tested in diabetic rats against standard drugs aspirin (anticoagulant) and metformin (antidiabetic). Rats were allocated into groups (n = 6) and administration was done orally, once daily for 2 weeks. The methanol extract and fractions of C. crepidioides at concentrations of 50, 100, and 200 mg/kg significantly prolonged the bleeding (58–200%), clotting (65–133%), prothrombin (176–441%), and activated partial thromboplastin (209–518%) times in diabetic rats compared to the control rats (LD50 ≥ 5000 mg/kg). Highest prolongation effects were recorded in the diabetic group treated with 100 mg/kg body weight of the hexane fraction. Plasma calcium concentration and platelet counts of C. crepidioides treated diabetic rats were significantly (P < 0.05) reduced compared to diabetic control rats, while the red blood cells (RBC), hemoglobin concentration, and packed cell volume (PCV) were significantly increased. This study showed that C. crepidioides possess anticoagulant and antianemic activities. The leaves can thus be a potential source of novel anticoagulant and nutraceutical for management of the thrombotic disorder in diabetes and other diseased states.

Hydroalcoholic extract of Achillea millefolium improved blood glucose, liver enzymes and lipid profile compared to metformin in streptozotocin-induced diabetic rats

BackgroundRecent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats.MethodsRats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes.ResultsThere was a significant reduction in blood glucose, serum liver enzymes, triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.ConclusionAchillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.

Antidiabetic and Antioxidant Effects of Acteoside from Jacaranda mimosifolia Family Biognoniaceae in Streptozotocin–Nicotinamide Induced Diabetes in Rats

BACKGROUND: Acteoside is a phenylethanoid compound isolated from Jacaranda mimosifolia D. Don leaves with a potential antidiabetic effect.&#x0D; OBJECTIVES: This study was designed to investigate the antidiabetic and antioxidant effects of acteoside in streptozotocin-nicotinamide (STZ-NA)-induced Type 2 diabetes in rats.&#x0D; METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of a single dose of STZ (52.5 mg/kg), 15 min following i.p. administration of NA (25 mg/kg). Rats were divided into six groups; Group I: Normal rat group received the vehicle, Group II: Diabetic control group, and Groups III-IV: Diabetic rat groups were treated by either oral acteoside (10, 20, and 40 mg/kg) or pioglitazone (30 mg/kg) for 21 consecutive days. Biochemical parameters were assessed in the serum and liver homogenates. Examination of liver sections for histopathology was also carried out.&#x0D; RESULTS: Acteoside treated rats showed significant lower levels of blood glucose, glycosylated hemoglobin, total cholesterol, triglycerides, and increased serum insulin compared to control diabetic rats. Furthermore, acteoside treated rats, in comparison to the diabetic control, demonstrated significantly reduced malondialdehyde, increased reduced glutathione liver contents, and attenuated pathological alterations in the liver. These effects were comparable to those caused by the standard antidiabetic drug, pioglitazone. In vitro, acteoside scavenged stable free radical 1,1-diphenyl-2-picrylhydrazyl.&#x0D; CONCLUSION: Acteoside could be considered as a potential therapeutic agent for type 2 diabetes mellitus. However, studying further mechanisms underlying its antidiabetic effect is recommended.

Farrerol ameliorates diabetic hepatopathy in rat model of type 2 diabetes mellitus via modulation of oxidativeinflammatory stress

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p &lt; 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p &lt; 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p &lt; 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p &lt; 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p &lt; 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in humans.&#x0D; Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet

EFFECT OF FLAXSEED EXTRACT ON THE LIVER HISTOLOGICAL STRUCTURE IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Introduction: Diabetes mellitus has become a serious warning to mankind health all over the world. The management goal of diabetes is to keep blood glucose levels as close as possible to healthy individuals. Medications used to treat diabetes are usually associated with complications and may cause different side effects. Many traditional anti-diabetic plants have become popular in the management of diabetes mellitus. Flaxseed has been used as traditional medicine for centuries. Objective: This study aimed to evaluate the hepatoprotective effects of flaxseed extract in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes mellitus was induced in Sprague-Dawley rats using a single injection of streptozotocin (60 mg/kg i.p.). The rats were divided into five groups of 8 rats each. Group NC, normal control rats; Group NF, normal rats treated with flaxseed extract (400 mg/kg); Group DC, diabetic control rats; Group DG, diabetic rats treated with glibenclamide (0.6 mg/kg); Group DF, diabetic rats treated with flaxseed extract (400 mg/kg); for 4 weeks. Results: There were significant increase in relative liver weight, blood glucose levels in DC group comparing to NC group (p<0.05). The disturbance of these parameters was ameliorated in DF and DG groups. Histological observation revealed congestion of central veins, degeneration of hepatocytes, and reduced glycogen granules in DC group. These pathological changes were ameliorated in the flaxseed extract and glibenclamide treated rats. Conclusion: Flaxseed extract may represent a candidate alternative treatment to control diabetes mellitus and its related hepatopathy.

Anti-diabetic, Haematinic and Anti-cholesterolmic Effects of Wheat (Triticum aestivum Linn.) Grass Juice Metabolites to Cure Alloxan Monohydrate induced type-1 Diabetes in Albino Rats

Introduction: From time immemorial therapeutic potential of Triticum aestivum grass is known. In present study an effort has been made to assess the hypoglycemic, anti-cholesterolmic and haematinic activity of Triticum aestivum grass juice in alloxan monohydrate induced experimental animal model. Materials and methods: Rats were acclimatized for 7 days in lab temperature. All animals were given standard water and pellet diet. Diabetes was induced in rats with the help of alloxan monohydrate (120 mg/kg body weight). After alloxan monohydrate injection rats were separated and treatment started with Triticum aestivum grass juice and insulin. Blood glucose level monitored with the help of glucometer. Results and discussion: A marked rise in fasting blood glucose as well as serum cholesterol level was observed in diabetic control rats when compared to normal control rats. Anti- hyperglycemic, anti-cholesterolmic and haematinic activity observed in Triticum aestivum grass juice administered rats on 7th, 14th, 21st and 28th days post treatment. Antihyperglycemic and anti-cholesterol mic activity was found less effective than that of insulin treatment group. Conclusion: It is hope that present investigation will be helpful in establishing a scientific basis for anti-diabetic, haematinic and anti- cholesterolmic effects in experimental animal models. The results are (<0.05) statistically significant.

MP04-06 THE IMPACT OF PNEUMOPERITONEUM ON RENAL FUNCTION AND THE DEVELOPMENT OF ACUTE KIDNEY INJURY

INTRODUCTION AND OBJECTIVE: Minimally invasive surgery is considered the gold standard approach for many urologic surgical procedures. However, it requires CO2 insufflation that causes elevated intra-abdominal pressure (IAP) and may result in adverse pulmonary, cardiovascular, gastrointestinal and renal changes. One of the main risk factors for developing post-operative acute kidney injury (AKI) is diabetes mellitus (DM). DM is considered an epidemic disease with rising incidence; hence the aim of this study was to examine whether the effect of pneumoperitoneum on renal function and the development of AKI is more pronounced in diabetic rats compared with normal rats. METHODS: Sprague Dawley rats were divided into two groups: Control (non-diabetic) rats (n=7) and diabetic rats (n=10). A Veress needle was used for CO2 inflation allowing the intra-abdominal pressure to be increased to desired levels of: 7, 10 and 14 mmHg for the duration of 45 minutes each. At the end, CO2 was deflated allowing pressure to decrease to 0 mmHg for 60 minutes (recovery phase). During each pressure point hemodynamic parameters were recorded and urine samples were collected for analysis of NGAL (neutrophil gelatinase associated lipocalin) a novel AKI biomarker. RESULTS: As shown in the Table, there were no statistically significant changes from baseline in urinary flow, urinary sodium excretion (UNaV), GFR, and RPF during 7 mmHg pressure in both groups. When the intra-abdominal pressure was further elevated, a significant deterioration of these parameters was recorded. This trend was more pronounced among the diabetic rats. When examining urinary NGAL, a linear correlation was observed between the intra-abdominal pressure and the biomarker level. This correlation was more significant in the diabetic group. CONCLUSIONS: The present study demonstrated a direct correlation between intra-abdominal pressure elevation and the development of AKI. Diabetic rats were more sensitive to the deleterious effect of pneumoperitoneum and urinary NGAL levels may be used as a future biomarker to predict post-operative AKI especially in diabetic patients.Source of Funding: None

Sperm Proteomics Analysis of Diabetic Induced Male Rats as Influenced by Ficus carica Leaf Extract

Diabetes mellitus is shown to bring negative effects on male reproductive health due to long-term effects of insulin deficiency or resistance and increased oxidative stress. Ficus carica (FC), an herbal plant, known to have high antioxidant activity and antidiabetic properties, has been used traditionally to treat diabetes. The objective of this study is to determine the potential of the FC leaf extract in improving sperm quality of streptozotocin (STZ) induced diabetic male rats from proteomics perspective. A total of 20 male rats were divided into four groups; normal (nondiabetic rats), negative control (diabetic rats without treatment), positive control (diabetic rats treated with 300 mg/kg metformin), and FC group (diabetic rats treated with 400 mg/kg FC extract). The treatments were given via oral gavage for 21 consecutive days. The fasting blood glucose (FBG) level of FC treated group demonstrated a significant (p &lt; 0.05) decrease compared to negative group after 21 days of treatment, as well as a significant (p &lt; 0.05) increase in the sperm quality parameters compared to negative group. Sperm proteomics analysis on FC treated group also exhibited the increase of total protein expression especially the proteins related to fertility compared to negative group. In conclusion, this study clearly justified that FC extract has good potential as antihyperglycemic and profertility agent that may be beneficial for male diabetic patients who have fertility problems.

Effects of Diabetes Mellitus on the Disposition of Tofacitinib, a Janus Kinase Inhibitor, in Rats.

Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

Antidiabetic and Antinephropathic Potential of Ajwa Pit &amp; Pulp (Phoenix dactylifera) in Alloxanized Diabetic Rats

Introduction: Generally in the world, diabetes is the most significant cause of deaths and morbidity. Blood glucose lowering agents possess remarkable adverse effects like weight gain and hypoglycemia and thus hindering the achievement of glycemic control. Since earliest times till today, herbal preparations have been utilized for management of diabetes and its complications. Aims &amp; Objectives: To investigate antihyperglycemic and nephroprotective effects of Ajwa pit and pulp in alloxanized - diabetic and nephropathic rats. Place and duration of study: This study was conducted at Postgraduate Medical Institute, Lahore for the duration of four weeks. Material &amp; Methods: Adult male rats (weighing 120-150 g), total of 32 were purchased and divided into 4 groups. The group1 was normal control whereas group2 was diabetic control. Diabetes was induced in groups 2, 3 and 4 with 150mg/kg single alloxan monohydrate1.P Injection. Groups 3 and 4 were given Ajwa pit and pulp rations for 4 weeks. Blood and urine samples were taken on zero and 4 weeks for fasting blood glucose, serum and urine biochemical variables for renal functions. Results: The results revealed that Ajwa pits significantly decreased serum levels of glucose (252±60 vs. 348±67 mg/dl), serum urea (38±7.0 vs. 63±9.6 mg/dl), serum creatinine (0.39±0.1 vs. 0.58±0.1 mg/dl) and microalbuminuria marker (7.8±1.7 vs. 9.0±2.2mg/l). Moreover it improved urine creatinine (14.0±2.9 vs.10.0±2.7 mg/dl) and creatinine clearance (0.226±0.08 vs 0.117±0.04 ml/min) when compared to diabetic control rats. Effect of Ajwa pulp was far less than Ajwa pit. Ajwa pulp did not significantly decrease serum levels of glucose (290±60 vs. 348±67 mg/dl), urea (51±9.5 vs. 63±9.6 mg/dl), creatinine (0.66±0.2 vs. 0.58±0.1 mg/dl) and microalbuminuria marker (8.3±2.0 vs. 9.0±2.2mg/l). Also there was no improvement in urine creatinine (11.1±1.6 vs. 10.0±2.7 mg/dl) and creatinine clearance (0.130±0.05 vs 0.117±0.04 ml/min) levels when compared to diabetic control rats. Conclusion: Ajwa pit possesses strong antihyperglycemic and protective effect in renal damage by prolonged diabetes mellitus. Highest polyphenols, bioflavonoids and antioxidants are presumed to be responsible for this effect.

Antidiabetic Effect of Aqueous Root Extract of Carica papaya L. in Alloxan-induced Diabetic Rats

Antihyperglycaemic effect of aqueous root extract of male Carica papaya L. (Family: Caricaceae) was investigated in alloxan-induced albino rats. 500 mg/kg body weight extract was administered by gavage orally twice daily for 7 days. Consequent upon induction of diabetes, the resulting raised levels of blood glucose, cholesterol, bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (AP) were significantly (p&lt;0.05) reduced after one week of administering the extract. In contrast, the significant decrease in total plasma protein of rats injected with alloxan were significantly (p&lt;0.05) increased following administration of extract compared to diabetic control rats. The results indicate the aqueous extract of male Carica papaya root ameliorated hyperglycaemia and hypercholesterolaemia lending credence to its folkloric use as treatment for diabetes mellitus. Furthermore, the extract ameliorated hepatic tissue injuries in the diabetic rats. Keywords: Carica papaya L., antihyperglycaemic, diabetic rats, aqueous, root, extract DOI: 10.7176/JNSR/10-6-01 Publication date: March 31 st 2020

Anti-diabetic activity of crude polysaccharide and rhamnose-enriched polysaccharide from G. lithophila on Streptozotocin (STZ)-induced in Wistar rats

The aim of the present study was to elucidate the anti-diabetic effects of the crude polysaccharide and rhamnose-enriched polysaccharide derived from G. lithophila on streptozotocin (STZ)-induced diabetic Wistar rats. Treatment with crude polysaccharide and rhamnose-enriched polysaccharide showed increases in body weight and pancreatic insulin levels and a decrease in blood glucose levels compared with control diabetic rats. The blood concentrations of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) decreased, and high-density lipoprotein (HDL) increased both in the crude polysaccharide- and rhamnose-enriched polysaccharide-treated rats. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels increased, and malondialdehyde (MDA) levels decreased in the livers, kidneys and pancreases of crude polysaccharide- and rhamnose-enriched polysaccharide-treated rats. Immunohistological examination further confirmed that restoration of the normal cellular size of the islets of Langerhans and the rebirth of β-cells were found to be greater in the body region than in the head and tail regions of the pancreas. The crude polysaccharide- and rhamnose-enriched polysaccharide-treated diabetic rats showed normal blood glucose levels and insulin production, and reversed cholesterol levels and enzymatic actions. Therefore, rhamnose-enriched polysaccharide from G. lithophila acts as a potent anti-diabetic agent to treat diabetes and can lead to the development of an alternative medicine for diabetes in the future.

Studies on Antidiabetic Activity of Atylosia Albicans in Streptozotocin-Induced Diabetic Rats

The present study was aimed to investigate the Antidiabetic effect of Atylosia Albicans extracts in streptozotocin-induced diabetes in Wistar rats. Rats have fasted overnight, and the plant extracts at doses 100 and 200 mg/kg were administered for 14 days. Streptozotocin was used to induce diabetes mellitus. The standard hypoglycaemic agent selected for this work was Glibenclamide (10 mg/kg). The different test solutions at doses 100 and 200 mg/kg of petroleum ether, ethyl acetate and methanolic extracts respectively were given a respective group of rats. The anti-diabetic potential was assessed by determining oral glucose tolerance, fasting blood glucose, Blood glucose levels, glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), high‑density lipoproteins (HDL), low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) were evaluated parameters. The methanolic extract with 200 mg/kg was more significant in anti-diabetic activity (P&lt;0.001) on the 14th day and also significantly decreased TG, TC, VLDL‑C, LDL‑C and HbA1c (P&lt;0.001) when compared to diabetic control rats. From the obtained results, it can be revealed that the methanolic extract of Atylosia Albicans has great potent antidiabetic activity. The results suggest that Triumfetta rotundifolia has anti-diabetic activity, thereby justifying its traditional use.