High-fat Diet-induced Diabetic Rats Research Articles

Naringin from sweet orange peel improves testicular function in high fat diet-induced diabetic rats by modulating xanthine oxidase/uric acid signaling and maintaining redox balance

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disorder affecting many organs, including the testis. Naringin from orange peel extract (OPE) is a flavanone with fertility-enhancing properties. Hence, this study was designed to establish the effect of naringin on T2DM-induced testicular dysfunction. Thirty male (30) Wistar rats were randomized into five groups control, diabetes, diabetes + naringin, diabetes + OPE, and diabetes + metformin. The administrations were via the oral route and lasted for 28 days.ResultsNaringin ameliorated T2DM-induced increase in FBS and decrease in serum insulin. It also abrogated T2DM-induced decrease in sperm quality, gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, prolactin, catalase, superoxide dismutase, and total antioxidant capacity. Furthermore, naringin prevented a T2DM-induced increase in malonaldehyde, tumor necrosis factor-alpha, C-reactive protein, xanthine oxidase (XO), and uric acid (UA), it was accompanied by the restoration of normal testicular histoarchitecture.ConclusionsNaringin prevented T2DM-induced testicular dysfunction by modulating XO/UA and restoring redox balance. Also, while the animals treated with OPE exhibited better ameliorative effects than their counterparts treated with naringin, the findings from this study showed that naringin would be a promising supplement for treating T2DM-induced male infertility.

Metformin promotes osteogenic differentiation and prevents hyperglycaemia-induced osteoporosis by suppressing PPARγ expression.

Metformin can prevent hyperglycaemia-induced osteoporosis and decrease the bone fracture rate, but the mechanism has not been fully elucidated. To reveal the mechanism by which metformin affects hyperglycaemia-induced osteoporosis, we treat a mouse osteoporosis cell model with metformin and find that osteoblast mineralization increases and PPARγ expression decreases. Single-cell mRNA sequencing analysis show that PPARγ is highly expressed in the bone tissue of osteoporosis patients, which highlights the role of PPARγ in osteoporosis. Furthermore, we find that PPARγ is the effector through which metformin prevents osteoporosis. We further examine the mechanism of PPARγ regulation and reveal that metformin regulates PPARγ expression through the AMPK pathway and that PPARγ affects osteoblasts through the endoplasmic reticulum stress (ERS) pathway. Moreover, we verify the association between the effect of metformin on bone metabolism and the expression of PPARγ in high-fat diet-induced diabetic rats. Thus, we identify and functionally validate that metformin prevents hyperglycaemia-induced osteoporosis by regulating the AMPK-PPARγ-ERS axis.

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring

The role of magnesium sulfate (MgSO4) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO4. Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4 and ICAM1 gene expressions in the kidney were also measured. MgSO4 or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO4 improved NOX4 and ICAM1 gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function.

Electronic Bypass for Diabetes: Optimization of Stimulation Parameters and Mechanisms of Glucagon-Like Peptide-1

ObjectivesIntestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats. Materials and MethodsThirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia. ResultsThe most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p < 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p > 0.05, IES + Exendin 9-39 vs sham-IES, N = 8). ConclusionIES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

P-Coumaric acid attenuates high-fat diet-induced oxidative stress and nephropathy in diabetic rats.

The prevalence of persistent hyperglycaemia during diabetes, impair antioxidant defence system and generate reactive oxygen species, which majorly contribute to its progression and associated complications. Phytochemicals were suggested to scavenge-free radicals and exert antioxidant effects required to improve insulin sensitivity and reduce the occurrence of diabetes-associated complications. We hypothesise that a phenolic phytochemical p-coumaric can reduce diabetes-induced oxidative stress and improve diabetes-associated nephropathy in rats. The aim of this study is to analyse the protective effects of p-coumaric acid against diabetes-induced oxidative stress and nephropathy in high-fat diet-induced diabetic rats. The oral feeding of p-coumaric acid (20mg/kg for 12weeks) was found to significantly decrease the elevated levels of blood glucose in high-fat diet-induced type 2 diabetic rats. p-Coumaric acid treatment also decreases the kidney weight whilst increasing the total body weight of diabetic rats. Furthermore whilst evaluation of the different renal functioning tests, p-coumaric acid significantly improves histopathological changes and the levels of urea, creatinine and uric acid in serum of diabetic rats, which was otherwise elevated under diabetic conditions. Our results also highlight that p-coumaric acid is an efficient compound with antioxidant properties and improves the diabetes-induced change in lipid peroxidation and activities of antioxidant enzymes: catalase, glutathione-S-transferase and superoxide dismutase. p-Coumaric acid thus possesses the potential to prevent diabetic nephropathy by reducing oxidative stress and can thus serve as a potential drug target for pharmaceutical companies.

Goat Milk Improves Glucose Homeostasis via Enhancement of Hepatic and Skeletal Muscle AMP-Activated Protein Kinase Activation and Modulation of Gut Microbiota in Streptozocin-Induced Diabetic Rats.

Previously, the metabolic benefits of goat milk consumption in high-fat diet-fed rats are demonstrated. However, the effects are only reported in one animal model and the involvement of gut microbiota is not investigated. The aim of this study is to investigate the effects of goat milk consumption on glucose homeostasis and gut microbiota in streptozocin (STZ)-induced diabetic rats. STZ-induced diabetic rats are fed with three dosages of goat milk: 2.5, 5, and 10g kg-1 . Parameters related to glucose homeostasis, hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, and gut microbiota are investigated. The dose of 10g kg-1 exerts more metabolic benefits. Goat milk consumption improves fasting glucose levels, glucose tolerance, insulin sensitivity, and promotes hepatic and skeletal muscle AMPK activation in STZ-injected diabetic rats. Goat milk modulates gut microbiota, increases the relative abundance of Lactobacillus, and augments levels of propionic and butyric acids. This study demonstrates the metabolic benefits of goat milk consumption in STZ-induced diabetic rats, which is consistent with the previous observations in high-fat diet-induced diabetic rats. Furthermore, this study elucidates the modulation of gut microbiota by goat milk, which likely mediates the metabolic effects of goat milk.

Effects of Pterostilbene isolated from Pterocarpus marsupium on High Fat Diet induced Diabetic Rats

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. The present study tested the anti-diabetic and hypolipidemic potential of pterostilbene isolated from Pterocarpus marsupium plants on high fat diet-induced diabetic rats. The high-fat diet-fed rats showed increased serum glucose, cholesterol, triglycerides and insulin resistance (p is less than 0.05). However, treating the animals with pterostilbene different biochemical parameters like glucose tolerance, glycogen content, glucose homeostatic enzymes like glucose-6-phosphatase and hexokinase, adipocytes differentiation, and the expression profiles of different genes regulating carbohydrate and lipid metabolism were improved significantly (p is less than 0.05). Further, pterostilbene was found to demonstrate dual regulation activities for peroxisome proliferators-activated receptors (PPAR) (both PPARα and PPARγ). In conclusion, these results show that pterostilbene acts as a potent antidiabetic molecule. Hence further in-depth mechanistic studies are warranted to use this phytochemical as a medicine.

Effect of polyherbal drug on oxidative stress and insulin resistance in high-fat diet-induced type 2 diabetic rats

ABSTRACT Many traditional plants have been used to fight life-threatening diseases such as diabetes, atherosclerosis and cancer. These plants have been shown to possess antioxidant activities, decrease the diabetes nuisance. The effect of 250 mg/kg b.wt of polyherbal drug (PHD) was investigated on high-fat diet-induced diabetic rats and impact of PHD administration was observed. The blood biochemical parameters such as glucose, insulin, hemoglobin, HbA1c, lipid profile and plasma antioxidants were evaluated. The increased levels of blood glucose, cholesterol, triglycerides and low-density lipoprotein cholesterol were noticed. In contrast, the levels of insulin and HDL-cholesterol were diminished. The oral administration of PHD showed a decrease in glucose level, cholesterol, triglycerides and LDL-cholesterol, whereas an increase in insulin level and HDL-cholesterol were recorded. What’s more, the antioxidant enzymes in diabetic control rats showed significantly decreased activities of SOD, catalase, glutathione peroxide activities and reduced glutathione (GSH) compared to treated diabetic rats and the extent of LPO. These results showed that our formulated PHDs have possessed antioxidant potential. The effect produced by the PHD on various parameters was comparable to that of Metformin – a standard anti-diabetic drug.

Assessment of the antidiabetic potentiality of glyburide loaded glyceryl monostearate solid lipid nanoparticles

The high rate homogenisation techniques was used for preparing glyburide loaded glyceryl monostearate solid lipid nanoparticles (Glb-SLNs) to improve the drug's solubility and oral bioavailability. It was mediated through pseudo-ternary phase diagrams to optimize the surfactant/co-surfactant ratio. The optimized Glb-SLNs were characterized by FT-IR spectroscopy, DSC, powder X-ray diffraction study and SEM analysis. In rat skeletal muscle cells (L6 myocytes) and in streptozotocin and high-fat diet-induced diabetic rats, anti-diabetic activity was evaluated. Flow cytometry analysis has accessed the effects of glucose uptake performed by the 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2- deoxyglucose (2-NBDG) in L6 myotubes. In normal rats and diabetic rats, parameters such as the blood glucose level, serum insulin, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), lipid peroxidase, catalase, glutathione, and HbA1c levels were assessed. Glb-SLNs at a dose of 50 μM showed a relative increase in relative fluorescence intensity of 92.5% to represent the glucose uptake potentiality. In vivo results revealed that the treatment with SLNs of glyburide (Glb-SLNs) normalized blood-glucose levels and serum biochemical parameters as compared with those of STZ controls. The protective effect was further confirmed by histopathological examination of the liver. These animals showed a comparable histopathological regeneration on Glb-SLNs treatment. These positive results demonstrated the success of the proposed SLNs approach in enhancing glyburide oral bioavailability and confirmed its potential as an effective system for diabetes treatment.

Effect of Raw and Cooked Ginger (Zingiber officinale Roscoe) Extracts on Insulin Sensitivity in Normal and High-fat Diet-induced Diabetic Rats

Few studies have determined the effect of different ginger extracts on insulin sensitivity, very few have explored the effect of raw extract of this spice on this parameter while the effect of cooked ginger extract (the form in which the spice is commonly consumed) is yet to be ascertained. This experimental study was therefore designed to determine the effect of raw and cooked ginger extracts on insulin sensitivity in normal and high-fat diet-induced diabetic rats. Ginger rhizomes were washed, peeled, wet-milled and sieved without adding water to obtain the raw extract. The raw extract was boiled for 1 hour to obtain the cooked extract. Seventy male albino rats of weight range 120-160g were divided into seven groups (n=10) and designated thus: ND2C-non-diabetic control; ND2R-non-diabetic rats given raw ginger extract (2ml/kg body weight); ND2Co- non-diabetic rats given cooked (boiled) ginger extracts; D2C-diabetic control; D2R- diabetic rats given raw ginger extract; D2Co- diabetic rats given cooked ginger extract; and D2D-diabetic rats given metformin (anti-diabetic drug)-200mg/kg body weight. Diabetes was induced in the diabetic groups by feeding the animals with high-fat diet (HFD) for 12 weeks to mimic Type 2 diabetes. Ginger extracts and the drug were administered as a daily oral dose for 4 weeks after diabetes induction. Insulin sensitivity (Insulin Tolerance Test) was determined before and after diabetes induction and at the end of the 4 weeks extracts administration using standard analytical method. Mean data were analyzed using ANOVA at p ≤ 0.05. Baseline Insulin Sensitivity (IS-%/min) in all the groups ranged from 2.2 to 2.4. After 12 weeks feeding, the IS in the three groups fed normal diet ranged from 1.9 to 2.1 while in the four groups fed HFD Insulin Sensitivity ranged from 0.1 to 0.3. Four weeks administration of raw and cooked ginger extracts did not significantly alter IS in normal rats while in diabetic rats raw, cooked ginger extracts and metformin significantly increased IS (%/min) to 2.1, 1.2 and 1.7 respectively relative to control which was 0.1. Insulin Sensitivity was maintained within the normal level in normal rats that were given raw and cooked ginger extracts while the raw extract was more effective than the cooked extract in increasing insulin sensitivity to normal level in diabetic rats. Both raw and cooked ginger extracts improved insulin sensitivity in high-fat diet-induced diabetic rats but the raw extract was more effective, hence, ginger in both forms may be applicable in the management of Type 2 diabetes. Human trial is hereby recommended.

Dietary Ginger Extracts Enhanced Glucose Uptake by Muscle and Adipose of Normal and Diabetic Rats via Mimicry of Insulin Action

The mechanism for the blood glucose lowering effect of different ginger extracts is yet to be clearly understood, that of raw ginger extracts has been sparsely explored while the mechanism for the cooked ginger extract, the form in which it is mostly consumed, has not been delved into. This study was therefore designed to determine the effect of raw and cooked ginger (Zingiber officinale Roscoe) extracts on glucose uptake by the muscle and adipose of normal, streptozocin-induced and high-fat diet-induced diabetic rats. Fresh ginger rhizomes were washed, peeled, milled and sieved without adding water to obtain the raw extract. A portion of this was boiled for 1 hour to give the cooked extract. Matured male albino rats (140) were divided into two major groups with 70 rats in each group. Group A was further divided into 7 sub-groups (n=10) 40 of which were rendered diabetic with intraperitoneal injection of streptozocin (60mg/kg body weight) to mimic Type 1 diabetes while in Group B Type 2 diabetes was induced with a 12 week consumption of High-Fat Diet (HFD). The remaining 30 rats in each group were left to remain non-diabetic/ normal. Ginger extracts were administered as a daily oral dose for 4 weeks after diabetes induction. The animals were the sacrificed and glucose uptake by the muscle and adipose tissue was determined using standard analytical procedure. Mean data were compared using Least Significant Difference at p≤ 0.05. It was clearly evidenced that both raw and cooked ginger extracts significantly enhanced and increased glucose uptake by the muscle and adipose tissues even in the absence of insulin, hence, mimicking insulin action. Ginger in both raw and cooked forms may therefore be beneficial in the prevention and management of diabetes mellitus. Human trial is hereby recommended.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats.

Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus (T2DM), aim of this study was evaluating the influance of regular swimming on serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in high-fat diet-induced diabetic rats. Fourty male Wistar rats were randomly divided into control, diabetic, exercise and diabetic-exercise groups (n = 10). Diabetes was induced by high-fat diet and streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, rats were anestatized and blood samples and pancreatic tissues were collected and used for evaluation of CRP, IL-6, TNF-α and pancreatic histopatholology. Our results showed significantly increase in lymphocytes, monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these parameters significantly reversed to control levels by induction of swimming (p < 0.01). In diabetic group, the levels of CRP, IL-6 and TNF-α increased (p < 0.01), and swimming decreased these factors significantly. Histopathological results of this study also showed that swimming can prevent damage induced by diabetes. The present study indicates that swim training is associated with improved inflammation and inflammatory mediators and pancreatic damage.

Role of chrysin on expression of insulin signaling molecules.

Background:Currently available drugs are unsuccessful for the treatment of tye-2 diabetes due to their adverseside-effects. Hence, a search for novel drugs, especially ofplant origin, continues. Chrysin (5,7-dihydroxyflavone) is a flavonoid, natural component of traditional medicinal herbs, present in honey, propolis and many plant extracts that hasbeen used in traditional medicine around the world to treat numerous ailments.Objective:The present study was aimed to identify the protective role of chrysin on the expression of insulin-signaling molecules in the skeletal muscle of high fat and sucrose-induced type-2 diabetic adult male rats.Materials and Methods:The oral effective dose of chrysin (100 mg/kg body weight) was given once a day until the end of the study (30 days post-induction of diabetes) to high fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, lipid peroxidation (LPO) and free radical generation, as well as the levels of insulin signaling molecules and tissue glycogen in the gastrocnemius muscle were assessed.Results:Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (IR, IRS-1, p-IRS-1Tyr632, p- AktThr308), glucose transporter subtype 4 [GLUT4] proteins and glycogen concentration. Serum insulin, lipid profile, LPO and free radical generation were found to be increased in diabetic control rats. The treatment with chrysin normalized the altered levels of blood glucose, serum insulin, lipid profile, LPO and insulin signaling molecules as well as GLUT4 proteins.Conclusion:Our present findings indicate that chrysin improves glycemic control through activation of insulin signal transduction in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic male rats.

Molecular approach to identify antidiabetic potential of Azadirachta indica.

Background:Azadirachta indica (Neem) is a medicinal plant, used in Ayurveda for treating various diseases, one of which is diabetes mellitus. It is known to possess antiinflammatory, antipyretic, antimicrobial, antidiabetic and diverse pharmacological properties. However, the molecular mechanism underlying the effect of A. indica on insulin signal transduction and glucose homeostasis is obscure.Objective:The aim was to study the effects of A. indica aqueous leaf extract on the expression of insulin signaling molecules and glucose oxidation in target tissue of high-fat and fructose-induced type-2 diabetic male rat.Materials and Methods:The oral effective dose of A. indica leaf extract (400 mg/kg body weight [b.wt]) was given once daily for 30 days to high-fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose oxidation in gastrocnemius muscle were assessed.Results:Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (insulin receptor, insulin receptor substrate-1, phospho-IRS-1Tyr632, phospho-IRS-1Ser636, phospho-AktSer473, and glucose transporter 4 [GLUT4] proteins), glycogen concentration and glucose oxidation. The treatment with A. indica leaf extract normalized the altered levels of blood glucose, serum insulin, lipid profile and insulin signaling molecules as well as GLUT4 proteins at 400 mg/kg b.wt dose.Conclusion:It is concluded from the present study that A. indica may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

Efficacy of Ginger (Zingiber officinale Roscoe) Extracts in Lowering Blood Glucose in Normal and High Fat Diet-induced Diabetic Rats

Even though the hypoglycemic effect of various extracts of ginger had been delved into exhaustively the similar effect of the cooked form of the spice is yet to be ascertained. This is of vital importance since ginger is mostly consumed in cooked form in various dishes. Hence, the objective of this study is to determine the efficacy of raw and cooked ginger extracts in lowering blood glucose in normal and high fat diet-induced diabetic rats, an experimental model of Type 2 diabetes which is the most prevalent type of the disease. Male Albino rats (63) were divided into seven groups and designated thus: Group 1 – normal negative control, Group 2 – normal rats given raw ginger extract, Group 3 - normal rats given cooked ginger extract, Group 4 - diabetic control, Group 5 –diabetic rats given raw ginger extract, Group 6 – diabetic rats given cooked ginger extract and Group 7 – diabetic rats given Metformin. The diabetic groups were fed high fat diet for 12 weeks after which the 4 weeks extracts administration commenced Fasting blood glucose was determined before and after the 12 weeks diet introduction and at the 2nd and 4th weeks of extracts’ administration by using ACCU-CHEK Active Glucometer, Roche, Germany. ANOVA and Least Significant Difference were used for statistical analyses. There was no significant difference between. Raw ginger extract and Metformin normalized fasting blood glucose (FBG) in the diabetic rats because there was no significant difference (p<0.05) between these two groups and the normal negative control at 4 weeks extracts and drug administration. The cooked extract did not normalize the blood glucose but lowered it by 35%..The two extracts had similar hypoglycemic effect (24% reduction, p<0.05) in normal rats at 2 weeks and 4 weeks of administration. Hence raw ginger extract is as effective as Merformin in normalizing FBG but the cooked form may require a longer period to exert similar effect..Even though the extracts lowered the FBG below normal in normal rats this may not lead to clinically threatening hypoglycemia.