Alloxan-induced Type Research Articles

Hypoglycemic, hypolipidemic and antioxidant potential of Myrcia pubipetala in an animal model of type 1 diabetes

Myrcia genus plants, like Myrcia pubipetala, traditionally used as hypoglycemic agents, hold promise for Type 1 Diabetes Mellitus (DM1) research but need more comprehensive chemical and pharmacological investigation. This is an experimental study involving controlled administration of treatments to a group of rats to assess their effects compared with a control group, investigating the effects of M. pubipetala on alloxan-induced Type 1 Diabetes Mellitus in rats. After the induction of diabetes, the rats received the hydroalcoholic extract (HAE) or aqueous fraction (AF) (25, 50, 100, or 150 mg kg-1) of M. pubipetala, or water. The results showed that diabetic rats presented cell damage in kidneys, oxidative stress, and high levels of glucose and triglycerides in their plasma and erythrocytes. The HAE (150 mg kg-1), per se, reduced lipid and protein oxidation, and the AF (150 mg kg-1) decreased lipoperoxidation. AF (150 mg kg-1), per se, decreased triglyceride levels. Conclusion: treatment with HAE and AF reduced oxidative damage, positively modulated antioxidant defenses, and exerted hypoglycemic and hypolipidemic effects, representing a potential adjuvant treatment for diabetes.

Umbilical Cord Blood Mesenchymal Stem Cells Mitigated Diabetic Hepato-Renal Insufficiency in Alloxan-Induced Type 1 Diabetes in Dogs: Biochemical and Histopathological Approach

Umbilical Cord Blood Mesenchymal Stem Cells Mitigated Diabetic Hepato-Renal Insufficiency in Alloxan-Induced Type 1 Diabetes in Dogs: Biochemical and Histopathological Approach

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes

PurposeTo evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI.MethodsTwenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests.ResultsAt baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide – pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively).Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

Serotonin transporter imaging agent as a probe for β-cells of pancreas

ObjectiveDiabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [125I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). MethodsIn vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. ResultsIn vitro cell studies showed that the concentration of [125I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [125I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. ConclusionsThe SERT imaging agent, [125I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.

Insulin secretory actions of polyphenols of Momordica charantia regulate glucose homeostasis in alloxan-induced type 2 diabetic rats

Abstract Objective Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and antidiabetic effects of an 80% ethanolic extract of M. charantia (EEMC) fruit, as well as the underlying molecular mechanism involved and preliminary phytochemical screening. Methods The insulin secretion was measured using clonal pancreatic BRIN-BD11 β-cells and isolated mouse islets. The ability of EEMC to inhibit carbohydrate digestive enzymes and glucose absorption and to scavenge free radicals was assessed via starch digestion, glucose diffusion, and 2,2-diphenyl-1-picrylhydrazyl assay methods. The effects of EEMC on a variety of metabolic parameters were evaluated in alloxan-induced type 2 diabetic rats, including lipid profile. Finally, a preliminary phytochemical screening was conducted to identify the active phytoconstituents. Key findings EEMC increased insulin release through the KATP-dependent/cyclic adenosine monophosphate pathway, which depolarizes the β-cell membrane and elevates intracellular calcium. It also inhibited glucose absorption and free radicals, suggesting its potential to delay gastric emptying, attenuate oxidative stress, and reduce inflammatory cytokines. In vivo studies showed that EEMC improves oral glucose tolerance, food intake, fasting blood glucose, plasma insulin, and lipids and promotes intestinal motility. The active phytoconstituents in EEMC, such as flavonoids, alkaloids, tannins, saponins, steroids, and glycosides, are likely responsible for these effects. Conclusion The antihyperglycemic properties of EEMC indicate that it might be a promising candidate for diabetes management. However, additional study into the application of M. charantia in type 2 diabetes is essential.

Hepatorenal Protective Functions of Coconut Water in Alloxan-Induced Type 1 Diabetes Mellitus

Coconut water is a natural product reported to contain antioxidant compounds with beneficial health effects. This study aimed to evaluate the antidiabetic effect of mature coconut water on some biochemical parameters of liver and kidney functions, and histological architecture of the pancreas in alloxan-induced diabetic rats. Twenty-four (24) Wistar rats were randomly divided into four groups, (n=6). Group I (negative control) rats were fed with rat chow and drinking water ad libitum and did not receive alloxan. Group II (positive control) received a single intraperitoneal dose of 150mg/kg body weight of alloxan to induce type 1 diabetes mellitus. Groups III and IV received a single intraperitoneal dose of 150mg/kg body weight of alloxan and were treated with 1ml/kg of mature coconut water for 3 weeks and 2mg/kg of glibenclamide for 3 weeks respectively by oral administration. On day 21, blood samples were collected for liver and kidney function tests. Liver function tests for Group II showed elevated aspartate transaminase (AST), alkaline phosphatase (ALP), albumin, total protein, total bilirubin, and low alanine aminotransferase (ALT) (p&lt;0.05). When compared with Group II, Group III showed elevated liver function parameters except ALT that was reduced (p&lt;0.05). Group IV showed elevated AST, total bilirubin, and reduced ALT, ALP, albumin, and total protein (p&lt;0.05). Kidney function tests showed that rats in Group II had significantly high creatinine, urea, bicarbonate, potassium, and sodium (p&lt;0.05). Group III had lowered creatinine, potassium levels, but with elevated urea, bicarbonate, and sodium levels (p&lt;0.05). Group IV had lowered creatinine, urea, bicarbonate, potassium levels, but with elevated sodium levels (p&lt;0.05). This study indicates that mature coconut water can be included in the treatment regimen for diabetes mellitus due to its hepatorenal protective functions.

Antioxidant, antihyperglycemic, and antihyperlipidemic properties of Chimonanthus salicifolius S. Y. Hu leaves in experimental animals: modulation of thioredoxin and glutathione systems, renal water reabsorption, and gut microbiota.

Excessive calorie intake and physical inactivity have dramatically increased nutrient overload-associated disease, becoming a global public health issue. Chimonanthus salicifolius S. Y. Hu (CHI) is a homology plant of food and medicine in China and shows several health benefits. This work investigated the antioxidant activity, the alleviating effects, and the mechanism of action on diabetes and hyperlipidemia of CHI leaves. Results showed that CHI leaves infusion displayed in vitro antioxidant activity measured by ABTS and ferric reducing antioxidant power methods. In wild-type Kunming mice, CHI leaves infusion consumption activated the hepatic antioxidant enzymes, including glutathione reductase, glutathione S-transferase, glutathione peroxidase and thioredoxin reductase as well as thioredoxin reductase 1. In alloxan-induced type 1 diabetic mice, CHI leaves infusion ameliorated diabetic symptoms, including polyuria, polydipsia, polyphagia and hyperglycemia, in a dose-dependent and time-course manners. The mechanism involved CHI leaves up-regulating renal water reabsorption associated protein - urine transporter A1-and promoting the trafficking of urine transporter A1 and aquaporin 2 to the apical plasma membrane. Despite this, in high-fat diet-induced hyperlipidemic golden hamsters, CHI leaves powder did not significantly effect on hyperlipidemia and body weight gain. This might be attributed to CHI leaves powder increasing the calorie intake. Interestingly, we found that CHI leaves extract containing a lower dose of total flavonoid than CHI leaves powder pronouncedly reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum in golden hamsters fed a high-fat diet. Furthermore, CHI leaves extract elevated the diversity of gut microbiota and the abundance of Bifidobacterium and Ruminococcaceae_UCG-014. It also decreased the abundance of Lactobacillus at the genus level in golden hamsters fed a high-fat diet. Overall, CHI leaves benefit oxidative stress prevention and metabolic syndrome amelioration in vivo.

DEVELOPMENT OF MICROCAPSULES BASED ON COMBINED ANTIDIABETIC SUBSTANCE: PHARMACOLOGICAL CHARACTERISTICS

The comparative assessment results of the hypoglycemic activity of a combined preparation containing microcapsules with a phytocomposition consisting of Glycyrrhiza glabra L. extracts, a dry extract of Galega officinalis L., Mentha piperita L., and gliclazide, are discussed in the article. Methods for obtaining microcapsules with an original PEG-6000 shell are described.The aim of the study was to develop an optimal technology for obtaining microcapsules with a PEG-6000 shell containing a combined antidiabetic substance, and conduct its detailed pharmacological study on the model of type 2 diabetes mellitus, to conduct a detailed comparative pharmacological study of a microencapsulated antidiabetic composition with a shell based on PEG-6000, including gliclazide and a sum of phytoextracts on the model of type 2 diabetes mellitus.Materials and methods. As the main objects of the study, microcapsules with a PEG-6000 shell were obtained using methyl miristate as the base liquid. The capsules contained the amount of plant extracts in their composition: a dry extract of Glycyrrhiza glabra L., a dry extract of Galega officinalis L., a dry extract of Mentha piperita L., and gliclazide. The study of a hypoglycemic activity was carried out after a single administration of drugs to the animals with alloxan-induced type 2 diabetes mellitus. The cumulative effect assessment of the drugs was carried out within 14 days with a test for the resistance to oral glucose on days 7 and 14.Results. Microcapsules with the original shell were obtained by dispersion in a liquid-liquid system with the adjustment of some technological stages. The effect of the drugs under study on the glycemic profile in the rats with an experimental model of type 2 diabetes mellitus was investigated. A comparative evaluation of the pharmacological effect was carried out with a separate and combined use of microencapsulated preparations.Conclusion. The rationality of combining phytocomponents and a synthetic antidiabetic agent in microcapsules has been proven. The obtained results testify to the rationality of plant extracts combination and a synthetic hypoglycemic agent – gliclazide in microcapsules.

Effect of Teneligliptin, and Teneligliptin Combined with Gabapentin on Alloxan-Induced Diabetic Neuropathy in Albino Mice

Diabetic neuropathy is a nerve disorder manifested by different faceted condition affecting up to half of individuals with persistent diabetes. Symptoms associated with this disease such as nerve palsy, painful polyneuropathy, thoracoabdominal neuropathy, autonomic neuropathy, diabetic amyotrophy, mononeuropathy multiplex, caused by motor, sensory, and autonomic nerve dysfunction which affects peripheral nervous system, gastrointestinal, pain receptors, urogenital, and cardiovascular system. In this study, type 2 diabetes was induced with alloxan in albino mice. After induction, drug treatment was initiated on the day 15, with different regimen on different group of mice that is teneligliptin, sitagliptin, combination of teneligliptin, and gabapentin. After investigation on day 21, 28, 35, and 42 found significantly improved glycemic control, paw jumping response, and grip strength (P &lt; 0.001). Mice treated with different regimen on day 21, 28, 35, and 42 were observed significant increase in blood protein (P &lt; 0.001). Alloxan caused marked nerve cell degeneration, teneligliptin and sitagliptin showed tissue regeneration and neutral effect on body weight. In the conclusion, treatment with teneligliptin and teneligliptin combined with gabapentin results an increase in pain sensitivity, grip strength, neural protection, and reverses the alteration of biochemical parameters but neutral effect on body weight in alloxan-induced type 2 diabetic mice.

Carvone’s Hypoglycemic and Hypolipidemic Potent Activity Via Regulation Insulin-Induced Genes in Diabetic Hyperlipidemic Rats

Carvone is a monoterpene and component of many essential oils from medicinal plants. Our research intended to evaluate the therapeutic efficacy of carvone in the handling of diabetes and hyperlipidemia in alloxan-induced type 2 diabetics. Alloxan (120 mg/kg) was administered intraperitoneally to male albino rats to induce diabetes as a single dose after diabetes, followed by two weeks of feeding the hypercholesterolemic atherogenic diet to develop hyperlipidemia. For one month, carvone (50 mg/kg) was administered orally to diabetic hyperlipidemic rats. Metformin, a common oral hypoglycemic medication, and atorvastatin, a standard oral hypolipidemic drug, were used to compare the findings. Our findings showed a reduction in blood glucose levels, low-density lipoprotein, cholesterol, and triglyceride. Upon administration of carvone, the encoded proteins (Insulin-induced gene-1and insulin-induced gene-2) were evaluated, which prevent Sterol regulatory-element binding proteins from being proteolytically activated. These transcription factors promote cholesterol and fatty acid production in the liver and other tissues. Histopathological alterations in pancreatic tissue were among the biomarkers chosen for hypoglycemic and hypolipidemic examinations. These findings suggested that carvone may be hypoglycemic and hypolipidemic potent activity by regulating insulin-induced genes.

The Hypoglycemic and Hypolipidemic Effect of 5- Naphthalidin-2, 4 Thiazolidinedione derivatives in Alloxan Induced Type II Diabetic Model

Objective: The present study was undertaken to study antidiabetic and antihyperlipidemic potentials of 5- naphthalidin-2, 4-thiazolidinediones derivatives and its interaction with rosiglitazone in alloxan-induced diabetic rats. Methods: Diabetes was induced in male swiss albino rats by single intramuscular injection of alloxan (0.15 mg/Kg i.m) and NIDDM-rats received 4b, 4c or 4d (36 mg/Kg, p.o). Fasting blood glucose (FBG) levels were measured by glucose-oxidase &amp; peroxidase reactive strips. Serum biochemical parameters such as total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by Duncan's Multiple Range Test (DMRT). Results: The results revealed that 4b, 4c and 4d showed promising results by lowering the blood glucose. Moreover, 4c compound displayed high efficiency for lowering lipid profiles compared to others. Conclusion: These results suggest that taking 5- naphthalidin-2, 4 TZD orally twice/day is a valuable treatment for Non insulin dependent diabetes mellitus (NIDDM) and hypolipidemic agent. They exert their effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.

Effect of Vildagliptin on the Level of P-Glycoprotein Expression in Normal Conditions and Alloxan–Induced Type 2 Diabetes Mellitus

INTRODUCTION: Vildagliptin is one of the drugs of choice in the treatment of type 2 diabetes mellitus (DM). In the literature review, no study has reported the effect of vildagliptin on the expression level of the transporter protein P-glycoprotein (P-gp, ABCB1 protein).&#x0D; AIM: To assess the in vivo effects of vildagliptin on the level of Р-gp expression in normal conditions and experimental alloxan-induced type 2 DM.&#x0D; MATERIALS AND METHODS: Type 2 DM was induced by a single intravenous injection of freshly prepared alloxan monohydrate solution in citrate buffer (pH = 4.0) at a dose of 80 mg/kg. Glucose content (mmol/L) was determined by the glucose oxidase method using Human kit (Germany) and insulin content (U/mL) by radioimmunoassay technique using Immunotech kit (Czech Republic). As an express method for the determination of glucose levels in the whole blood, OneTouch UltraEasy electrochemical glucose monitor (USA) was used. The level of P-gp expression in rabbit tissues (i.e., jejunum, liver, kidney, and cerebral cortex) was evaluated by the indirect histochemical method. After preliminary treatment, the histological material was embedded in paraffin. Antigens were retrieved before the immune-staining reaction. Then, the sections were incubated with primary antibodies to P-gp (ABCB1 antibody, middle region; 0.1 mL [Aviva Systems Biology ARP51326-P050, USА]). For immune staining, a polymer detection system with a peroxidase label (Leica Microsystems, Germany) was used. The cell nuclei were stained with hematoxylin. Photos of the micropreparation were captured using Canon Power Shot G5 digital camera with 400 magnification. Digital images were analyzed and processed using ImageJ and IHC Profiler plugin designed for quantitative immunohistochemical analysis. The results obtained from healthy animals, animals with alloxan-induced DM, healthy animals administered vildagliptin, and animals with modeled DM administered vildagliptin were compared.&#x0D; RESULTS: After day 14 of administration to healthy rabbits and day 5 of vildagliptin discontinuation (5 mg/kg), no statistically significant changes in P-gp expression in the aforementioned tissues and the levels of basal and postprandial insulin and blood glucose were noted. After the 14-day therapy of alloxan-induced type 2 DM with vildagliptin (5 mg/kg), a statistically significant recovery of expression of the P-gp expression in the jejunum, liver, and kidney was reduced due to the underlying pathology. In addition, the values of healthy rabbits and statistically significant normalization of the insulin and blood glucose levels were observed. On day 5 of drug cancellation, significant inhibition of P-gp expression in the jejunum, liver, and kidney was noted again, and there was a significant reduction of postprandial insulin and blood glucose. No significant alterations of ABCB1 protein expression in the hematoencephalic barrier were noted during the studied periods.&#x0D; CONCLUSION: The administration of vildagliptin (5 mg/kg) to rabbits with alloxan-induced type 2 DM promotes the recovery of P-gp expression in the jejunum, liver, and kidney, which were reduced due to the underlying pathology. Meanwhile, its administration to healthy animals had no significant effect on the expression of P-gp.

Dyslipidaemia of Alloxan-Induced Type 1 Diabetes Mellitus in Dogs is attenuated by Ethanolic Extracts of Anogeissus Leiocarpus Stem Bark

Introduction: The effect of ethanolic extract of Anogeissus leiocarpus stem bark on dyslipidaemia induced by diabetes mellitus (DM) was investigated, since enhanced pro-synthetic hypoglycaemic drugs did not effectively control dyslipidemia of DM, apart from causing toxicity and resistance. Materials and Methods: Twelve adult Nigerian indigenous dogs were placed in 4 groups of 3 each, namely non diabetic (ND); diabetic untreated (DU); diabetic treated with insulin (DI) and diabetic treated with extract (DE). Body weights and lipid profiles were measured during a four-week period. Results: Significant percentage body weight decreased in DU (50.21 %) throughout the period of study with continuous increase in body weight in ND (46.96 %). In DI and DE there were initial decreases in body weights (11.08% and 14.54% respectively) which significantly increased (23.53 % and 32.30 % respectively) by the fourth week. Lipid profiles revealed significant (P &lt; 0.002) increases in triglycerides, total cholesterol and low-density lipoproteins (LDL) in DU group when compared with the DE group. There was also a significant (P &lt; 0.002) decrease in high density lipoprotein (HDL) in the DU when compared to DE, DI and ND groups. Conclusion: The ethanolic extract of Anogeissus leiocarpus stem bark attenuated the dyslipidaemia produced in alloxaninduced type 1 diabetes mellitus in Nigerian indigenous dogs.

Antidiabetic Activity of Gomphogyne bonii Gagnep. Extract against High-Fat Diet and Alloxan-Induced Type 2 Diabetes in Mice.

So far, diabetes mellitus has become a health threat to society all over the world. Especially, people with diabetes have always coped with complications related to this disease and unexpected side effects of synthetic drugs. Thus, there has been a current trend for researchers to find out new natural ingredients which were safer and still effective in the treatment of diabetes. Gomphogyne bonii Gagnep. extract (G. bonii extract) was an herbal-derived product of the Pharmacy Department, Vietnam University of Traditional Medicine. This study was designed to assess the antidiabetic effect of G. bonii extract on a high-fat diet (HFD) and alloxan-induced diabetes in mice. Mice were first fed a high-fat diet for 8 weeks and then given an intraperitoneal injection of alloxan (ALX) at the dose of 180 mg/kg b.w. After the diabetic mice model was successfully established, mice were administered orally with G. bonii extract at two doses of 4 mL/kg b.w/day and 12 mL/kg b.w/day for 2 weeks. The results revealed that G. bonii extract at both doses ameliorated the effects of ALX on the concentration of glucose, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) and microhistological images of livers. Besides, the antidiabetic effect of G. bonii extract at the dose of 12 mL/kg b.w/day was better than that at the dose of 4 mL/kg b.w/day. This suggested that G. bonii extract could be a potential agent for treating diabetes mellitus in clinical practice.

Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse.

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Elevated serum sialic acids, a potent biomarker of alloxan-induced type 1 diabetes in dogs by ethanolic extract of Anogeissus leiocarpus.

This study investigated serum sialic acids for a predictive and diagnostic biomarker of diabetes mellitus (DM) in dogs and its prognostic value with ethanolic extract of Anogeissus leiocarpus. Four groups of 3 dogs were used; non-diabetic controls (ND), diabetic-untreated (DU), diabetic insulin-treated (DI) and diabetic extract-treated (DE). Free serum sialic acids (FSSA) and erythrocyte surface sialic acids (ESSA) were assayed in all groups, pre-and post-induction of hyperglycaemia and results were presented as means ± standard error of means (SEM) and subjected to ANOVA using Tukey's post-hoc tests with GraphPad Prism® statistical package. FSSA increased in DU and plateaued at third week (61.8 ± 0.41μg/ml), (P < 0.002) with additional 38.2μg/ml (62%) generated, coinciding with hyperglycaemia. FSSA of DI increased but declined to 22.3 ± 1.55μg/ml. Extract of Anogeissus leiocarpus effectively modulated FSSA in DE as increased value declined to 21.4 ± 0.78μg/ml. Pre-induction DU ESSA (8.27 ± 0.11μg/ml) significantly (P < 0.002) decreased by third week (2.33 ± 1.49μg/ml), coinciding with hyperglycaemia. Strong negative correlation coefficient (r = -0.92) occurred between DU's FSSA and ESSA and ND (P < 0.03). Sialic acid expression in dog's insulin dependent diabetes mellitus (IDDM) is 18% lower than normal. Extract of A. leiocarpus restored ESSA completely. ESSA cleaved in DU, 5.94μg/ml (72%), could not account for the extra FSSA (32.26μg/ml); liver and kidneys are contributors. FSSA predicts canine DM.

Protective Effects of Moderate Intensity Static Magnetic Fields on Diabetic Mice.

The purpose of this study was to investigate the effects of moderate-intensity static magnetic field (SMF) on diabetic mice. We studied the effects of SMF on blood glucose of normal mice by starch tolerance and glucose tolerance tests. Then, we evaluated the effects of SMF on blood glucose of diabetic mice by establishing alloxan-induced type 1 diabetic mice and high-fat diet + streptozotocin (STZ)-induced type 2 diabetic mice. The results showed that different magnetic field intensities and blank control did not affect the blood glucose of normal mice. After starch and glucose administration, different magnetic fields could improve the glucose tolerance of normal mice, and this was obvious in the600 mT group. In the experiment of type 1 diabetic mice induced by alloxan, the results showed that different magnetic field intensities could improve the starch tolerance of mice, and that in the 400 mT group was obvious. In the experiment of type 2 diabetic mice induced by a high-fat diet + STZ, the 400 mT group could reduce food intake and water consumption in the later period. The 600 mT group could improve the starch tolerance of mice. The 400 and 600 mT groups could reduce fasting blood glucose. At the same time, total cholesterol and triglyceride decreased in different magnetic field intensities, and the 600 mT group could significantly increase the serum insulin content of mice. In summary, the results of this study suggest that SMF has a protective role in diabetic mice. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

SYNTHESIS, BIOLOGICAL EVALUATION AND DOCKING STUDIES OF NON HEPATOTOXIC 5-SUBSTITUTED THIAZOLIDINE-2, 4-DIONES AS ANTIDIABETIC, ANTI-HYPERLIPIDEMIC, ANTI-OXIDANT AND CYTOTOXIC AGENTS

A series of eleven thiazolidine-2, 4-dione (TZD) derivatives, were synthesized and characterized by FT-IR, 1 H NMR and mass spectral analysis. All the synthesized TZD derivatives were screened for their in vitro and in vivo anti-diabetic and antioxidant, activities and cytotoxicity. In vivo antihyperglycemic effect was assessed by measuring plasma glucose (PG) levels in alloxan-induced type II diabetic rat models. The compound 4h exhibited better blood glucose lowering activity than the standard drug rosiglitazone. The synthesized TZD derivatives were evaluated for hepatotoxicity and pancreatic tissue studies. Antioxidant activity was evaluated by DPPH method and H2 O2 method. Compounds 4a and 4b exhibited potent antioxidant activity. Among the tested compounds for cytotoxicity using MTT assay method, compound 4i exhibited better viability and cytotoxicity activity. Thiazolidinedione derivatives were evaluated for their affinity towards target PPARg, using rosiglitazone as the reference compound molecular docking visualization through FlexX docking program. From selected anti-diabetic targets, the proposed derivatives exhibited better interaction with PPARγ receptor, where rosiglitazone showed docking score of -19.891 kJ/ mol, compound 4h exhibited highest docking score of -31.6068 kJ/mol. The study showed that all the studied compounds were showing higher docking score when compared to control drug rosiglitazone and it could be a remarkable starting point to evaluate structure activity relationships to develop new lead molecules with potential anti-diabetic activities.

Anti-diabetic Activity of Chrysophyllum albidum (G. Don) Stem Bark in Alloxan-induced Type 1 Diabetic Female Wistar Rats

Anti-diabetic activity of aqueous extract of Chrysophyllum albidum stem bark (AECASB) in female Wistar rats was investigated to confirm or refute the purported use and the underlying mechanism of action of C. albidum stem bark in the management of type 1 diabetes in Nigeria traditional medicine. Seventy female rats (180.60 ± 8.50 g) were assigned into seven groups. Rats in Group 1 (non-diabetic) were orally administered 1 mL of distilled water, while animals in Groups 2-7 were made diabetic and orally administered 1 mL of distilled water, 2.5 mg/kg body weight (bwt) of glibenclamide, 25, 50, 100 and 200 mg/kg bwt of AECASB, once daily for 14 days, respectively. Fasting blood glucose (FBG) levels of the rats were determined on days 0, 1, 4, 7, 10 and 14. Other biochemical, hematological parameters and pancreas histology of the rats were also determined/examined. The 25 mg/kg bwt of AECASB produced the most significant (p &lt; 0.05) reversal on the alloxan treatment-induced increases in FBG, biochemical and hematological parameters and regenerated the pancreas. In conclusion, the 25 mg/kg bwt of aqueous extract of C. albidum stem was the effective in the management of diabetes and might have acted via regeneration of the pancreas, enhancement of glucose utilization and reduction of blood glucose.&#x0D; Keywords: Type 1 diabetes mellitus; fasting blood glucose; Chrysophyllum albidum; Sapotaceae;