Responses In Diabetic Rats Research Articles

Immunomodulatory activity of kersen leaf extract (Muntingia calabura) on diabetic rats: analysis of immune response

The immune response to high blood glucose levels leads to an inflammatory response and also produces inflammation mediators. Immunomodulatory functions of Kersen (Muntingia calabura) need further enhancement to ensure that its benefits are more widely recognized by the public. This study aims to determine the immunomodulatory activity of Kersen leaf in inducing and modulating the immune response in diabetic rats. This study was an experimental laboratory with a pre-and post-test with a control group design. The subjects were 30 white rats (Rattus Novergicus Wistar Strain), were treated with extract M. calabura dose 1 (100 mg/kg bw/day), dose 2 (200 mg/kg bw/day), dose 3 (300 mg/kg bw/day). For clinical evaluation, three control groups were formed, including a Normal Control Group, a Diabetes Mellitus (DM) Positive Group, and a DM Positive Group treated with Anti-Diabetic Drugs. The highest amount of IFN-γ concentrations were found in the DM positive control group + antidiabetic drugs (710.3 ± 27.2 ng/mL). The highest number of Nitrit Oxide (NO) concentration was found in the DM positive control group (103.7 ± 10.2 µmol/L). The highest average amount of pancreatic β cell regeneration was found in the normal control group. The DM positive control group and the treatment group had a significant difference (p < 0.05) It means that there is a significant difference in the data of all treatment groups, or these three groups have anti-diabetic activity by repairing or preventing damage to the pancreas organ in DM rats. This study revealed that M. calabura possesses immunomodulatory activity, capable of inducing and modulating immune responses in diabetic rats.

Effect of Vitamin K2 on Blood Rheology and Vascular Responses in Diabetic Rats

Background/aim: Diabetes is manifested by endothelial dysfunction and an imbalance between vasoconstriction and vasodilation. The aim of our study is to examine the effect of vitK2 application on vascular and rheological parameters in a rat diabetes model. Materials and methods: A total of 60 male Wistar Albino rats were used to examine vascular responses and hemorheological parameters. A total of 6 groups were: control (C), control+vehicle (Cv), control+vitK2 administered (C + K2), diabetes (D), diabetes+vehicle (Dv), and diabetes+vitK2 (D + K2) group. After the animals were sacrificed, blood and vascular samples were taken and the contraction and relaxation responses of the aorta and erythrocyte deformability and aggregation were examined. Results: When KCl dose-response curves are evaluated; Increased vasoconstriction response was found in the Dv group compared to the Cv group. The increase in vasoconstriction observed in the Dv group decreased with the application of vit K2. D+vitK2 group thoracic aorta contraction responses returned to Cv group levels. In response to increasing cumulative doses of Phe, a significant increase in vasoconstriction response was observed in the Dv group compared to the Cv group. VitK2 application reduced the Phe-mediated contractile response, which was increased in the Dv group, and returned the contraction response to Cv conditions except for two intermediate Phe doses. In the Dv + K2 group, a significant decrease was observed in the aggregation index, which was tended to increase. Conclusion: Considering the cardiovascular complications frequently observed in diabetes, it can be suggested that vitK2 therapy may yield positive outcomes in diabetes.

Exploring the underlying mechanism of ethyl acetate extract of Annona muricata leaves via the NRF2 and NF-ΚB pathway in type 1 diabetic Wistar rats

Type 1 diabetes mellitus is an autoimmune disorder characterized by the destruction of pancreatic beta cells, leading to impaired insulin production and regulation. Recent research has shown that medicinal plants with antioxidant and anti-inflammatory properties hold promise as potential therapeutic agents for managing complications of the disease. The aim of this study is to investigate the anti-diabetic, antioxidant, and anti-inflammatory effect of ethyl acetate extract of Annona muricata leaves in streptozotocin (STZ)-induced diabetes in Wistar rats. Thirty five (35) male Wistar rats weighing 150-180g were used for this experiment. Group 1 (Normal control), Group 2 (STZ 40 mg/kg only Diabetic control), Group 3 (STZ+ metformin 500mg/kg bw), Group 4 (STZ + ethyl acetate extract 250 mg/kg bw), Group 5 (STZ + ethyl acetate extract (500 mg/kg bw). Fasting blood samples were collected by cardiac puncture for glucose estimation and liver tissues excised for both biochemical and molecular studies. The study demonstrated the extract's ability to modulate the NF-κB pathway, leading to the suppression of inflammatory responses in diabetic rats. These findings suggest that the ethyl acetate extract of A. muricata leaves may ameliorate type 1 diabetes by promoting antioxidant defense and reducing inflammatory processes through the NRF2 and NF-κB pathways. This research sheds light on the potential of natural compounds as adjunct therapies for type 1 diabetes and provides a foundation for further investigations into the development of novel treatments targeting oxidative stress and inflammation in autoimmune diabetes.

Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats.

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes's impairment of spatial learning memory. Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines. Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide. Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.

Zwitterionic Pluronic analog-coated PLGA nanoparticles for oral insulin delivery

In recent years, zwitterionic materials have drawn great attention in oral drug delivery system due to their capacity for rapid mucus diffusion and enhanced cellular internalization. However, zwitterionic materials tend to show strong polarity that was hard to directly coat hydrophobic nanoparticles (NPs). Inspired by Pluronic coating, a simple and convenient strategy to coat NPs with zwitterionic materials using zwitterionic Pluronic analogs was developed in this investigation. Poly(carboxybetaine)-poly(propylene oxide)-Poly(carboxybetaine) (PCB-PPO-PCB, PPP), containing PPO segments with MW > 2.0 kDa, can effectively adsorb on the surface of PLGA NPs with typical core-shell spherical in shape. The PLGA@PPP4K NPs were stable in gastrointestinal physiological environment and sequentially conquered mucus and epithelium barriers. Proton-assisted amine acid transporter 1 (PAT1) was verified to contribute to the enhanced internalization of PLGA@PPP4K NPs, and the NPs could partially evade lysosomal degradation pathway and utilize retrograde pathway for intracellular transport. In addition, the enhanced villi absorption in situ and oral liver distribution in vivo were also observed compared to PLGA@F127 NPs. Moreover, insulin-loaded PLGA@PPP4K NPs as an oral delivery application for diabetes induce a fine hypoglycemic response in diabetic rats after oral administration. The results of this study demonstrated that zwitterionic Pluronic analogs-coated NPs might provide a new perspective for zwitterionic materials application as well as oral delivery of biotherapeutics.

L-limonene reduces aortic artery atherosclerosis by inhibiting oxidative stress/inflammatory responses in diabetic rats fed high-fat diet.

Atherosclerosis, a leading cause of mortality worldwide, is driven by multiple risk factors such as diabetes. Oxidative stress and inflammation assist interrelated roles in diabetes-accelerated atherosclerosis. Thereby, treatment of diabetic atherosclerosis from an oxidative stress/inflammatory perspective seems to be a more effective modality to prevent and delay plaque formation and progression. This study aimed to evaluate the effects of l-limonene (LMN) on oxidative stress/inflammatory responses in the aortic artery of diabetic atherosclerosis-modeled rats. Male Wistar rats (n = 30, 250-280 g, 12 weeks old) were used to establish a diabetic atherosclerosis model (8 weeks) using high-fat diet/low-dose streptozotocin. LMN (200 mg/kg/day) was administered orally, starting on day 30th before tissue sampling. Plasma lipid profiles, aortic histopathological changes, atherogenic index, aortic artery levels of oxidative stress markers (manganese superoxide dismutase, glutathione, and 8-isoprostane), inflammatory markers (tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10), and expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, Sirtuin 1 (SIRT1), and p-p65/p65 proteins were evaluated. The administration of LMN to diabetic rats improved lipid profiles, aortic histopathological morphology, and atherogenic index (P < 0.05 to P < 0.001). It also increased enzymatic antioxidant activities, decreased 8-isoprostane level, suppressed inflammatory response, upregulated p-AMPK and SIRT1 proteins, and downregulated p-p65 protein (P < 0.05 to P < 0.01). Inhibiting the AMPK through the administration of compound C significantly abolished or reversed the positive effects of LMN in diabetic rats (P < 0.05 to P < 0.01). LMN treatment had dual anti-oxidative and anti-inflammatory actions against atherosclerosis in the aortic artery of diabetic rats. Atheroprotection by LMN was mediated partly through modulation of AMPK/SIRT1/p65 nuclear factor kappa B signaling pathway. LMN appears to be a promising anti-atherosclerotic modality to improve the quality of life in diabetic patients.

Scrophulariae Radix-Atractylodes sinensis pair and metformin inhibit inflammation by modulating gut microbiota of high-fat diet/streptozotocin-induced diabetes in rats.

Type 2 mellitus (T2DM), a chronic metabolic disorder, causes severe impairment of patients' quality of life and has attracted global attention. Many studies have suggested the importance of the gut microbiota in the occurrence of T2DM. The Scrophulariae Radix and Atractylodes sinensis (XC) pair, recommended in traditional Chinese medicine (TCM), have been used for treating diabetes for many years. However, research on the role of the XC pair in modulating gut microbial communities is lacking, but it is important to elucidate the underlying mechanism. In this study, we detected bacterial communities by high-throughput 16S rRNA gene sequencing. The results showed that XC + MET reduced postprandial hyperglycemia and inflammatory response in diabetic rats more effectively than metformin (MET) alone. The XC + MET treatment reshaped the intestinal microbial composition of diabetic rats. XC can help MET regulate carbohydrate, amino acid, and lipid metabolism, particularly the insulin signaling pathway. This research would help elucidate potential mechanisms and the treatment methods.

The effects of supplementation of Nannochloropsis oculata microalgae on biochemical, inflammatory and antioxidant responses in diabetic rats.

Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementation of Nannochloropsis oculata microalgae (NOM) on the inflammatory and antioxidant responses in diabetic rats. Sixty male rats were divided into six groups as diabetic and non-diabetic rats receiving 0, 10 and 20 mg/kg of body weight of NOM daily for 21 days. Body weight, the serum concentrations of insulin and glucose and the tissue concentrations of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione peroxidase (GPx) were assessed. The results showed that induction of diabetes significantly reduced the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while increasing the concentrations of glucose, MDA, IL-1β, IL-6, NF-κB and TNF-α. Daily oral administration of NOM (10 and 20 mg/kg) significantly maintained the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while preventing the increase in the concentrations of glucose, MDA, IL-1β and TNF-α. In conclusion, diabetes caused inflammation and oxidation while NOM worked as a natural anti-inflammatory and antioxidant compound.

STIM/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction Through Modulation of Rat and Human Penile Tissue Contractility and in vivo Potentiation of Erectile Responses

Stromal interaction molecule (STIM)/Orai calcium entry system appears to have a role in erectile dysfunction (ED) pathophysiology but its specific contribution to diabetic ED was not elucidated. To evaluate STIM/Orai inhibition on functional alterations associated with diabetic ED in rat and human penile tissues and on in vivo erectile responses in diabetic rats. Rat corpus cavernosum (RCC) strips from nondiabetic (No DM) and streptozotocin-induced diabetic (DM) rats and human penile resistance arteries (HPRA) and corpus cavernosum (HCC) from ED patients undergoing penile prosthesis insertion were functionally evaluated in organ chambers and wire myographs. Erectile function in vivo in rats was assessed by intracavernosal pressure (ICP) responses to cavernous nerve electrical stimulation (CNES). Expression of STIM/Orai elements in HCC was determined by immunofluorescence and immunoblot. Functional responses in RCC, HCC and HPRA and STIM/Orai protein expression in HCC. In vivo erectile responses to CNES. Inhibition of Orai channels with YM-58483 (20 µM) significantly reduced adrenergic contractions in RCC but more effectively in DM. Thromboxane-induced and neurogenic contractions were reduced by STIM/Orai inhibition while defective endothelial, neurogenic and PDE5 inhibitor-induced relaxations were enhanced by YM-58483 (10 µM) in RCC from DM rats. In vivo, YM-58483 caused erections and attenuated diabetes-related impairment of erectile responses. YM-58483 potentiated the effects of PDE5 inhibition. In human tissues, STIM/Orai inhibition depressed adrenergic and thromboxane-induced contractions in ED patients more effectively in those with type 2 diabetes. Diabetes was associated with increased expression of Orai1 and Orai3 in ED patients. Targeting STIM/Orai to alleviate diabetes-related functional alterations of penile vascular tissue could improve erectile function and potentiate therapeutic effects of PDE5 inhibitors in diabetic ED. Improving effects of STIM/Orai inhibition on diabetes-related functional impairment was evidenced in vitro and in vivo in an animal model and validated in human tissues from ED patients. Functional findings were complemented with expression results. Main limitation was low numbers of human experiments due to limited human tissue availability. STIM/Orai inhibition alleviated alterations of functional responses in vitro and improved erectile responses in vivo in diabetic rats, potentiating the effects of PDE5 inhibition. STIM/Orai inhibition was validated as a target to modulate functional alterations of human penile vascular tissue in diabetic ED where Orai1 and Orai3 channels were upregulated. STIM/Orai inhibition could be a potential therapeutic strategy to overcome poor response to conventional ED therapy in diabetic patients. Sevilleja-Ortiz A, El Assar M, García-Gómez B, et al. STIM/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction Through Modulation of Rat and Human Penile Tissue Contractility and in vivo Potentiation of Erectile Responses. J Sex Med 2022;19:1733-1749.

Effects of two workload-matched high intensity interval training protocols on regulatory factors associated with mitochondrial biogenesis in the soleus muscle of diabetic rats.

Aims: High intensity interval training (HIIT) improves mitochondrial characteristics. This study compared the impact of two workload-matched high intensity interval training (HIIT) protocols with different work:recovery ratios on regulatory factors related to mitochondrial biogenesis in the soleus muscle of diabetic rats. Materials and methods: Twenty-four Wistar rats were randomly divided into four equal-sized groups: non-diabetic control, diabetic control (DC), diabetic with long recovery exercise [4–5 × 2-min running at 80%–90% of the maximum speed reached with 2-min of recovery at 40% of the maximum speed reached (DHIIT1:1)], and diabetic with short recovery exercise (5–6 × 2-min running at 80%–90% of the maximum speed reached with 1-min of recovery at 30% of the maximum speed reached [DHIIT2:1]). Both HIIT protocols were completed five times/week for 4 weeks while maintaining equal running distances in each session. Results: Gene and protein expressions of PGC-1α, p53, and citrate synthase of the muscles increased significantly following DHIIT1:1 and DHIIT2:1 compared to DC (p ˂ 0.05). Most parameters, except for PGC-1α protein (p = 0.597), were significantly higher in DHIIT2:1 than in DHIIT1:1 (p ˂ 0.05). Both DHIIT groups showed significant increases in maximum speed with larger increases in DHIIT2:1 compared with DHIIT1:1. Conclusion: Our findings indicate that both HIIT protocols can potently up-regulate gene and protein expression of PGC-1α, p53, and CS. However, DHIIT2:1 has superior effects compared with DHIIT1:1 in improving mitochondrial adaptive responses in diabetic rats.

Clove (Syzygium aromaticum) ameliorates oxidative stress-induced inflammation and improves reverse cholesterol transport and paraoxonase 1 activity in diabetic rats

Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs. Accordingly, in the current study we have investigated the effect of clove on lipid metabolism, and on oxidative stress-induced inflammation response in diabetic rats. Diabetes was induced intraperitonially by a single injection of streptozotocin (STZ). The treated group received daily orally clove extract, for 4 weeks. Daily treatment by clove lowered significantly blood glucose, HbA1c levels and ameliorates the lipid profiles and showed increased PON1 activity. The study of lipid peroxidation showed that, the treatment with clove decreased TBARS levels in LDL fraction and in pancreas. Furthermore, in pancreas TNF-alpha and IL-1β levels were decreased in treated group. These results were confirmed by the histopathological assessments which clove treatment showed marked improvement of the destructive effect on pancreas islet cells induced by STZ. The present findings clearly demonstrated that clove could prevent many diabetic complications by reducing inflammation and oxidative damage. Thus, the effectiveness of clove in treating diabetes potentially may possibly due to presence of bioactive compounds.

Changes in gut microbiota of alloxan-induced diabetic rats in response to orally administered combined aqueous extracts of olive leaves and ginger

Gut microbiota characterization in Egyptian patients with hepatocellular carcinoma post-chronic hepatitis C virus genotype 4 infectionKarim Montasser, Heba Ahmed Osman, Hanan Abozaid, Mohammed H. Hassan, Abeer M. M. sabry

GR/NF-κB signaling pathway regulates hippocampal inflammatory responses in diabetic rats with chronic unpredictable mild stress

Clinical studies have shown that diabetes can present with underlying depression, and a combination of the two can lead to emotional, memory and cognitive disorders, closely associated with hippocampal neuroinflammation. However, the mechanism underlying the development of hippocampal neuroinflammation under the above condition remains elusive. The aims of this study were to explore the pathogenesis of diabetes combined with depression, and the effect of dexamethasone (Dex), a glucocorticoid receptor (GR) agonist, on hippocampal neuroinflammation in diabetic rats with chronic unpredictable mild stress (CUMS). Therefore, rats were intragastrically fed on a high-fat diet (10% cholesterol 10 ml/kg) for 14 days and thereafter injected with 38 mg/kg of streptozotocin on the 15th day to induce diabetes. Dex treatment of the diabetic and CUMS rats ameliorated the depression-associated behavior in the respective rats. Apart from enhanced depressive behavior, diabetes-depressed condition also up-regulated the expression of hippocampus microglia chemokine Ⅰ receptor (CX3CR1) and secretion of several pro-inflammatory factors, in particular, interleukin 1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor - α (TNF-α). Hematoxylin-eosin staining revealed inflammatory damages in the hippocampus. Western blot analysis further revealed repression of GR proteins converse to the nuclear factor kappa-B (NF-κB) proteins, which were up-regulated. Intriguingly, Dex reversed the above events by inhibiting inflammatory reactions in the hippocampus. Consequently, played an antidepressant effect in diabetic and CUMS model rats. Overall, findings of this research suggest that the physiopathology of diabetes with stress cormobity are mediated by inflammatory reactions in the hippocampus. In particular, the responses are associated with regulation of GR/NF-κB signaling pathway.

Renoprotective effects of tropisetron through regulation of the TGF-β1, p53 and matrix metalloproteinases in streptozotocin-induced diabetic rats

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Massonʼs trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-β1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-β1, p53, and expression of extracellular matrix metalloproteinases.

Therapeutic effects of different doses of prebiotic (isolated from Saccharomyces cerevisiae) in comparison to n-3 supplement on glycemic control, lipid profiles and immunological response in diabetic rats

BackgroundThe regular intake of fiber generates numerous health benefits. However, the efficacy depends on the duration of consumption and the ingested dose. Studies investigating the optimal dose are of interest to enable the inclusion of fiber in the routine treatment of diabetic patients.ObjectiveWe aimed to evaluate the effects of different doses of β-glucan (BG—isolated from Saccharomyces cerevisiae), in comparison to n-3 supplement, on the inflammatory and metabolic parameters of Wistar rats induced to diabetes by streptozotocin.MethodsForty animals were randomly divided into six groups receiving 0 mg/kg, 10 mg/kg, 20 mg/kg, or 40 mg/kg BG daily for 4 weeks or fish oil derivative [1000 mg/kg of omega-3 fatty acids (n-3)] for the same period. One additional group was composed of healthy controls. Serum metabolic and immunological parameters were evaluated by colorimetric and ELISA assays respectively. Histopathological analysis of the liver, small intestine and pancreas were also conducted. Significant changes due to BG intake were set into regression models with second-degree fit in order to estimate the optimal BG dose to achieve health benefits.ResultsThe animals that ingested BG had lower food and water intake (p < 0.05) than the negative control group (0 mg/kg). However, consumption was still elevated in comparison to healthy controls. Blood glucose and serum levels of total cholesterol, LDL-c, and TG (p < 0.05) reduced in comparison to diabetic animals without treatment (better or similar to n-3 group depending on dose), but did not reach normal levels (in comparison to healthy controls). HDL-c was not different (p > 0.05) among all groups. These reductions were already seen with the lowest dose of 10 mg/kg. On average, the serum levels of the hepatic enzymes ALT and AST were 40% and 60% lower in the BG groups in comparison to diabetic animals without treatment (better results than n-3 group). The group receiving 40 mg/kg reached similar values of healthy controls for ALT; whereas the same result occurred from the dose of 10 mg/kg for AST. The ideal dose, estimated from the mean of all metabolic parameters was approximately 30 mg/kg/day. Regarding the immunological profile, TNF-α significantly decreased in the BG groups compared to controls (p < 0.05), reaching better values than n-3 group and similar to healthy controls. No significant differences were found between the groups in IL-1β or IL-10 (p > 0.05). No histological changes were found in the pancreas, liver, or intestine due to treatment among diabetic animals.ConclusionsBG significantly reduced blood glucose as well as serum total cholesterol, LDL-c and TG. There was a hepatoprotective effect due to the reduction in ALT and AST and a reduction in TNF-α, indicating a modulation of the immune response. In general, BG effects were better than n-3 supplement (or at least comparable) depending on the dose.

The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats.

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) usingvarious inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K+ channels independently NO signalling pathway.

Changes in Serum Levels and Gene Expression of PGC-1α in The Cardiac Muscle of Diabetic Rats: The Effect of Dichloroacetate and Endurance Training.

Objective Physical activity leads to changes in the level of gene expression in different kinds of cells, including changes in mitochondrial biogenesis in the myocardium in diabetic patients. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a gene that plays an important role in regulating mitochondrial biogenesis. The purpose of this study was to investigate changes in serum levels and cardiac muscle expression of PGC-1α in diabetic rats in response to the administration of dichloroacetate (DCA) and endurance training. Materials and Methods In this experimental study, 64 male Wistar rats were selected and randomly divided into eight groups after induction of diabetes with streptozotocin (STZ). The endurance training protocol was performed on a treadmill for 6 weeks. Intraperitoneal injection of DCA of 50 mg/ kg body weight was used for the inhibition of Pyruvate Dehydrogenase Kinase 4 (PDK4) in the myocardium. Gene expression were measured using real-time polymerase chain reaction (PCR). One-way ANOVA and Tukey’s test were used to statistically analyze the data. Results The results of the study showed that PDK4 gene expression in the endurance training group, diabetes+endurance training group, diabetes+endurance training+DCA group and endurance training+DCA group was higher compared to the control group. Expression of PGC-1α was higher in the endurance training group compared to the control group but was lower compared to the control group in diabetes+endurance training+DCA group and diabetes+DCA group (P<0.05). ConclusionConsidering that PGC-1α plays an important role in mitochondrial biogenesis, it is likely that by inhibiting PDK4 and subsequently controlling oxidation of fatty acid (FA) in the heart tissue, oxidative stress in the heart tissue of diabetic patients will be reduced and cardiac efficiency will be increased.

Catecholaminergic and opioidergic system mediated effects of reboxetine on diabetic neuropathic pain.

Current data indicate that the noradrenergic system plays a critical role in neuropathic pain treatment. Notably, drugs that directly affect this system may have curative potential in neuropathy-associated pain. The aim of this study was to evaluate the potential therapeutic efficacy of reboxetine, a potent and selective noradrenaline reuptake inhibitor, on hyperalgesia and allodynia responses in rats with experimental diabetes. Furthermore, mechanistic studies were performed to elucidate the possible mode of actions. Experimental diabetes was induced by a single dose of streptozotocin. Mechanical hyperalgesia, mechanical allodynia, thermal hyperalgesia, and thermal allodynia responses in diabetic rats were evaluated by Randall-Selitto, dynamic plantar, Hargreaves, and warm plate tests, respectively. Reboxetine treatment (8 and 16mg/kg for 2weeks) demonstrated an effect comparable to that of the reference drug, pregabalin, improving the hyperalgesic and allodynic responses secondary to diabetes mellitus. Pretreatment with phentolamine, metoprolol, SR 59230A, and atropine did not alter the abovementioned effects of reboxetine; however, the administration of α-methyl-para-tyrosine methyl ester, propranolol, ICI-118,551, SCH-23390, sulpiride, and naltrindole significantly inhibited these effects. Moreover, reboxetine did not induce a significant difference in the rat plasma glucose levels. Our findings indicate that the antihyperalgesic and antiallodynic effects of reboxetine are mediated by the catecholaminergic system; β2-adrenoceptors; D1-, D2/D3-dopaminergic receptors; and δ-opioid receptors. The results suggest that this analgesic effect of reboxetine, besides its neutral profile on glycemic control, may be advantageous in the pharmacotherapy of diabetic neuropathy-induced pain.

Carnitine effects on serum and pancreas inflammatory response in diabetic rats

Carnitine effects on serum and pancreas inflammatory response in diabetic rats

Umbelliferone isolated from Zosima absinthifolia roots partially restored erectile dysfunction in streptozotocin-induced diabetic rats

Erectile dysfunction (ED) is a common problem in diabetic men, which affects the quality of life. Zosima absinthifolia (Vent.) Link (syn. Zosima orientalis Hoffm.) is the only member of Zosima genus growing in Turkey. Its fruits and aerial parts have been used in folk medicine as a sedative and digestive problems. This study aimed to investigate the possible beneficial effect of intracavernosal injection of umbelliferone isolated from Z. absinthifolia Link roots on ED of streptozotocin-induced diabetic rats. Adult Sprague–Dawley (n = 20) rats were divided into control and streptozotocin-induced diabetic groups. In vivo erectile responses were also repeated after intracavernosal injection of umbelliferone (1 µM). Umbelliferone-induced relaxant responses in the presence of inhibitors of nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were assessed in corpus cavernosum (CC) strips from control rats. The relaxant responses of CC strips from both groups were evaluated in the presence or absence of umbelliferone (100 μM). In vivo erectile responses in diabetic rats were significantly lower than in controls, which were partially prevented by umbelliferone. Umbelliferone resulted in a relaxation of CC in a concentration-dependent manner. NOS and cGMP inhibitors antagonized the umbelliferone-induced relaxations in CC. Acetylcholine, sodium nitroprusside, a phosphodiesterase type 5 inhibitor, sildenafil and electrical field stimulation-induced relaxation responses in diabetic CC strips were potentialized after pre-incubation with umbelliferone. In conclusion, intracavernosal administration of umbelliferone may prevent ED in diabetic rats by recovering of NO/cGMP pathway. These results may be supported by further studies using combinations of umbelliferone and phosphodiesterase type 5 inhibitors for the treatment of diabetic ED.