Function In Diabetic Rats Research Articles

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.

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

The Effect of Endurance Training Intensity on the Expression of Perlipin a Protein of Subcutaneous Adipose Tissue and Pancreatic B cells Function in Diabetic Rats

Objective: The aim of this study was to compare the three endurance training intensities on the expression of Perlipin A protein in subcutaneous adipose tissue and pancreatic B-cells function in male diabetic rats. Materials and Methods: In this study, 40 healthy male wistar rats were divided into five groups, including diabetic with low intensity endurance training, diabetic with moderate intensity endurance training, diabetic with high intensity endurance training, diabetic control and healthy control. After diabetic induction with streptozotocin, endurance training was performed with low intensity, moderate and severe for eight weeks, three sessions per week. The relative expression of Perilipin A was measured by western blot technique. Results: The results indicated a significant effect of endurance training with three intensities on serum levels of insulin and glucose and pancreatic B-cells function ( P -value: 0.001). Also the results showed that there was no significant difference between Perlipin A expression in healthy and diabetic control groups with endurance training groups (with low, moderate and high intensity) ( P -value: 0.07). Conclusion: However, Moderate and high intensity endurance training compared to low-intensity training can compensate for the loss caused by diabetes in the expression of the Perlipin A protein but the difference was not significant. It seems that more intensity endurance training lead to more increase in Perlipin A expression in diabetic rats.

Worsening Cardiac Autonomic Neuropathy on Progression to Type 2 Diabetes: Localized vs. Systemic Inflammation

Cardiac autonomic neuropathy (CAN) occurs early in the course of diabetes with significant cardiovascular risks. While linked to hyperglycemia, current understanding extends CAN development to pre‐diabetes. The instigating cause of CAN, its temporal progression, and responsiveness to treatment remain ill‐defined. Here, we used a rat model of mild metabolic challenge with delayed development of hyperglycemia to trace these parameters in different disease stages.Male Sprague Dawley rats (5–6 weeks old) were fed a mild hypercaloric diet (4.035 vs. 3 KCal/g) leading to hyperinsulinemia after 12 weeks, representing the prediabetic stage. Type 2 diabetes was induced by two consecutive injections of low‐dose streptozotocin (40 mg/kg) at weeks 8 and 9. Drug treatment (metformin 100 mg/Kg/day, pioglitazone 2.5 mg/Kg/day, insulin titrated to control glucose levels, or their combination) was started at week 10. CAN was assessed by estimating baroreceptor sensitivity using the vasoactive method. ELISA, immunohistochemistry, and western blotting were used to examine markers of structural deterioration, inflammation, and autophagy in serum, heart, and brainstem.CAN was detected in the prediabetic state as blunted bradycardic reflex to phenylephrine stimulation reflected by a decrease in the slope of the DMAP vs. DHR line. It progressed with the transition to diabetes to further parasympathetic deterioration and de novo sympathetic insult. Interestingly, diabetic sympathetic dysfunction was readily reversed by insulin treatment. While prediabetic parasympathetic dysfunction responded to treatment with non‐hypoglycemic, anti‐inflammatory doses of metformin or pioglitazone, this was not the case in diabetic rats. Worsened parasympathetic function in diabetic rats was only restored by combination treatments, with insulin and Met/Pio. Notably, whereas prediabetic dysfunction was associated with localized perivascular adipose inflammation, the exaggerated CAN observed in diabetes was accompanied by significant systemic inflammation manifesting as elevated serum IL‐1b levels. This was concomitant with centralization of inflammation presenting in the brainstem along with microglial activation and autophagy suppression. Significantly, only combination treatment produced a considerable decrease in serum IL‐1b, consistent with their corrective effect on CAN in diabetes. Moreover, hyperglycemic rats showed signs of focal cardiac ischemia and left ventricular dysfunction which were ameliorated with combination treatments. In a cellular framework, we showed that systemic inflammation, rather than metabolic stress, induced neuronal damage. Differentiated PC12 cells simulating sympathetic neurons only replicated the central manifestations observed in diabetic rats when exposed to diabetic rat serum as opposed to the altered serum insulin, glucose, and lipid levels.Our results highlight a temporal framework whereby deteriorating metabolic state leads to exaggerated CAN possibly related to the progression of localized adipose inflammation to a systemic inflammatory state affecting brainstem and cardiac function.Support or Funding InformationFunding by AUB‐FM grant #320148

Hepatic- and Renal protective Effects of Chrysophyllum albidum (African Star Apple) Fruit-Skin Supplementation on Streptozotocin-Induced Diabetic Rats

Chrysophyllum albidum commonly called African star apple, has been reported for its antidiabetic potential but its effect on liver and kidney functions in diabetic rats has not been well investigated. This study investigated effects of Chrysophyllum albidum fruit-skin (CAFS) supplemented diet on Streptozotocin-induced diabetic rats. Diabetes was induced intraperitonealy at a single dose of 50mg/kg bw of Streptozotocin (STZ). Forty male Wistar rats weighing averagely 170g were randomly divided into four groups of ten rats each; Group 1-Normal control, Group 2-Diabetic control, Group 3-Diabetic rats treated Glibenclamide, Group 4-Diabetic rats treated 70g/kg CAFS supplemented diet. After four weeks of treatment, the rats were sacrificed. Liver function biomarkers (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP)) activities, kidney function biomarkers (Creatinine and Urea), electrolyte ions (K + , Na + , HCO 3 - and Cl - ), total protein and bilirubin levels were measured in the plasma. The diabetic control exhibited hepato-renal dysfunction with significant (p<0.05) increase in the liver marker enzymes’ activities, total bilirubin, creatinine and urea concentrations while decreasing total protein, albumin and electrolyte ions levels compared with normal control group. Treatment with CAFS supplemented diet significantly (p<0.05) enhanced liver and kidney recovery by reducing the elevated activities of liver marker enzymes, reversed the increments in creatinine, urea and total bilirubin while increasing the concentration of total protein and restoring electrolyte ions concentrations to near normal values. CAFS supplemented diet has hepatic- and renal protective effects on STZ-induced diabetic rats. Thus, CAFS could be considered as therapeutic agent against the progression of diabetes complications. Keywords: Chrysophyllum albidum ; fruit-skin; liver markers; kidney markers; diabetes. DOI: 10.7176/JNSR/10-6-02 Publication date: March 31 st 2020

Effects of modified acidic fibroblast growth factor mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction on left ventricular systolic function in diabetic rats

Objective To investigate the effects of modified acidic fibroblast growth factor (MaFGF) mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction (UTMD) on left ventricular systolic function in early diabetes mellitus(DM) rats. Methods The nanoliposomes containing MaFGF(MaFGF-nlip) were prepared by reverse phase evaporation method. Among 60 male Sprague Dawley (SD) rats, 50 rats were randomly selected and were induced to be DM models by streptozotocin(STZ) through intraperitoneal injecting, the other 10 rats as control group. Then DM rats were randomly divided into 4 groups: DM model group, MaFGF solution group, MaFGF-nlip group and MaFGF-nlip+ UTMD group. After the successful induction of DM model, the intervention was performed twice a week.After 12 weeks of intervention, all rats underwent conventional echocardiography and velocity vector imaging (VVI). Left ventricular ejection fraction (LVEF) and left ventricular fraction shortening(LVFS) were measured by conventional echocardiography. The mean peak systolic radial velocity (Vs), radial strain (Sr) and radial strain rate (SRr) of six walls at the papillary muscle level were measured in left ventricular short-axis view by VVI. At last, myocardial tissue of all rats were stained with Sirius red to evaluate myocardial interstitial fibrosis. The level of myocardial apoptosis was evaluated by TUNEL staining, and the changes of myocardial ultrastructure were observed by transmission electron microscopy. Results The prepared MaFGF-nlip were more rounded, evenly dispersed, and of good stability and high encapsulation efficiency. Twelve weeks later after intervention, LVEF, LVFS, Vs, Sr and SRr in the DM model group were significantly lower than those in the control group (all P<0.05). LVEF, LVFS, Vs, Sr and SRr in the MaFGF-nlip+ UTMD group were significantly higher than those of the DM model group and other intervention groups (all P<0.05). The results of Sirius red staining and Tunel staining showed that CVF and AI in the DM model group were significantly higher than those in the control group (all P<0.05). For MaFGF-nlip+ UTMD group, CVF and AI were significantly decreased compared with the DM model group and other intervention groups(all P<0.05). According to the results of transmission electron microscopy, compared with the DM model group, the improvement of myocardial ultrastructure was the most obvious in the MaFGF-nlip+ UTMD group. Conclusions MaFGF delivered by using nanoliposomes combined with UTMD can improve the left ventricular systolic function in diabetic rats by inhibiting the myocardium cardiac fibrosis and reducing the cardiomyocyte apoptosis. Key words: Ultrasound-targeted microbubble destruction; Diabetic cardiomyopathy; Ventricular function, left; Nanoliposomes; Modified acidic fibroblast growth factor

Effect of Turkesterone on the Pancreas Histology and Function in Diabetic Rats

Effect of Turkesterone on the Pancreas Histology and Function in Diabetic Rats

Association of glucose homeostasis measures with heart rate variability (HRV) among hyperlipidemic rat model: protective role of Emblica officinalis

Background: Altered glucose homeostasis due to hyperlipidemia mainly revolves around pathophysiological effects of abnormal lipid levels and insulin resistance. Reduced HRV an indicator of cardiac autonomic function is connected with greater risk of cardiovascular diseases. Glucose homeostasis markers were related with reduced cardiac autonomic functions in diabetic rats but results reported were discordant with those without diabetes. Aims and objectives: Study aimed to assess relation between glucose homeostasis with HRV among hyperlipidemic rats and to assess protective glucose regulatory actions of Emblica officinalis on hyperlipidemic rats. Material and Methods: Ethanolic extract of Emblica Officinalis (EEO) was prepared. Rats were divided into four groups (n=6); group 1- Control (20% fat); group 2 (20% fat+ EEO 100 mg/kg/b w); group 3 (30% fat) and group 4 (30% fat + EEO 100 mg/kg/b w) for 21 days.Gravimetry and electrophysiological analysis (HRV and sympathovagal balance) were done. In vivo, tests on glucose regulatory system were conducted like fasting and postprandial glucose, fasting insulin levels and Oral Glucose Tolerance Test. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. ANOVA and Pearson's correlation was done to analyze the data. Results: Subchronic supplementation of EEO to hyperlipidemic rats showed a significant beneficial effect on altered glucose homeostasis. An electrophysiological evaluation revealed altered sympathovagal balance in hyperlipidemic rats which indicate cardiac autonomic malfunctions and found to be improved in EEO supplemented rats. A significant correlation was observed between HRV and glucose homeostasis. Conclusion: Impairment in glucose homeostasis due to High-fat diet is associated with altered heart rate variability. EEO supplementation found to be protective against high-fat diet-induced cardiac autonomic dysfunction and glucose metabolism.

Diyabete Bağlı Kognitif Bozukluk Sıçanların Hipokampüslerinde Nlrp3 ve Nitrotirozin Seviyelerinin Artışı ile İlişkilidir

Aim: Diabets mellitus is associated with impaired learning and memory. Neuroinflammation is a pathophysiological hallmark of diabetes which include production of cytokines. It was suggested that nitrative injury has been implicated in the pathophysiologic mechanism of diabetes. Nod-like receptor family pyrin domain-containing (NLRP) inflammasomes are important in the development of inflammatory response through production of IL-1β and IL-18. In the present study was aimed to examine the relationship between NLRP3, IL-1 β, nitrotyrosine levels and cognitive functions in diabetic rats. Material and Methods: The rats were randomly divided into 2 groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Body weight and blood glucose level were measured until euthanasia. Morris water maze (MWM) was used to evaluate the cognitive function in rats. Hippocampal NLRP3, IL-1 β and nitrotyrosine levels were measured. Results: The results showed that the elevated blood glucose was obseved in diabetic group. NLRP3 and nitrotyrosine levels were found to be increased in hippocampus of diabetic rats. There was no statsitical significance in the hippocampal IL-1β level with diabetes. In the MWM, diabetic rats spent more time to find the submerged platform when compared with control rats, implying a significant impairment of learning and memory, and this impairment was found to be statistically signifcant at day 5. Conclusion: Our results indicate that STZ induced diabetes causes learning and memory impairment in rats probably by generating nitrosative stress and increasing NLRP3 level in the hippocampus.

Electrochemical assessement of the therapeutic agent of dietary nitrite in streptozotocin induced diabetic rats based on Ni-Cu/nanotitania sensor

Nitrite compounds are very important in many industrials that may cause some significant problems, but in more or less cases it has useful effect. Therefore, the present study was carried out to shed the light on the effect of nitrite on streptozotocin (STZ) inducing diabetic rats. In this study, thirty-two male Wister rats were distributed into four groups (n= 8 per group): Group (1) control group; Group (2) normal rats received NaNO2 30 mg/kg body weight; Group (3) diabetic group rats received 45 mg/kg STZ intraperitoneal (IP); Group (4) diabetic rats treated daily with NaNO2 for three months. Serum from each group was collected from rat's blood samples to measure aminotransferase (AST), alanine aminotransferase (ALT), Urea, and Creatinine. A self-assembled nanostructure titania (TiO2) based surface similar to honey cells was synthesized by a simple, fast, low-cost procedure using the 2D electrochemical cell at sequence potential from 5 V to 30 V for 2 h followed by annealed method at 350°C and 750°C for 3 h. A linear sweep voltammetry electrochemical method was used to deposit the Ni-Cu nanoparticles on titania surface providing a highly sensing platform of Ni-Cu/nanotitania array. Both the degree of sensing (46 µA mM−1) for the electrode were calculated through low detection range from 0.00 to 0.35 mM of glucose via cyclic voltammetry and amperometery techniques. By increasing the glucose concentration through the detection range from 0.4 to 2.5 mM the sensitivity increased to 248 µA mM−1. This significant change indicates that the sensitivity of the electrode is suitable for diabetes measurements. We reported for the first electrochemical sensor fabricated from Ni-Cu/nanotitania to detect glucose level in real urine samples and we used this level as a marker for the effect of nitrite present in the drinking water. The results showed that the presence of low concentration of sodium nitrite can enhance the liver and kidney functions in diabetic rats and also lead to the decrease of the glucose concentration in urine. Additionally, Ni-Cu/nanotitania sensor also has stability, profitable good reproducibility and applicability that guarantee its value in the medical applications as in the environmental applications that has been proven previously.

Changes of myocardial function in diabetic rats and its mechanism

To investigate the role of calcium-sensing receptor (CaSR) in the decrease of cardiac function in type 2 diabetic rats. Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups. Rats in the diabetes group were fed with high-glucose and high-fat diet, and intraperitoneal injection of streptozocin (STZ,30 mg/kg) was conducted 4 weeks later to establish a type 2 diabetes model. Cardiac morphological changes were observed by HE staining, cardiac function was detected by echocardiography, and CaSR and PKC-αprotein expressions in cardiac tissue were detected by Western blot. Compared with the control group, the myocardium of diabetic rats showed irregular contraction zone, decreased expression of CaSR protein, increased expression of PKC-α protein, decreased systolic and diastolic functions, and gradually worsened with the prolongation of the course of the disease. Hyperglycemia inhibits the expression of CaSR protein in myocardium of diabetic rats by activating PKC-α, which can cause intracellular calcium disorder and lead to decreased cardiac function.

Evaluation of antioxidant potential of Emblica officinalis and Murraya koenigii and their role in modulation of cognitive function in diabetic rats

Background: Hyperglycaemia and hyperlipidaemia seen in diabetes mellitus result in oxidative stress and pose significant risk of cognitive decline that may lead to Alzheimer’s disease. Approved anti-diabetic drugs have so far failed to demonstrate anti-oxidant and anti-hyperlipidemic activity, apart from saroglitazar. Therefore, this study was done to find a suitable anti-diabetic drug that possesses anti-hyperglycaemic, anti-oxidant and anti-hyperlipidemic activities and can reverse cognitive decline.Methods: Emblica officinalis (250 mg/kg, p.o. and 500 mg/kg, p.o.) and Murraya koenigii (250 mg/kg, p.o. and 500 mg/kg, p.o.) were chosen to study these activities in Wistar rats. Diabetes was induced by single intraperitoneal injection of streptozotocin [STZ] (50 mg/kg). Fasting blood glucose levels and lipid profile were measured on day 1 and day 30 of the experiment. Cognitive function was assessed by measuring transfer latency (TL) on elevated plus maze, step-down latency (SDL) on passive avoidance apparatus and retention latency (RL) and quadrant time (QT) in Morris water maze. Oxidative stress was assessed at end of study by measuring brain MDA and GSH levels. Cholinergic marker of cognition, AChE was measured in brain at end of study.Results: Both E. officinalis and M. koenigii showed dose dependent anti-hyperglycemic, anti-hyperlipidemic and anti-oxidant effects in diabetic rats with 500 mg/kg dose showing significantly higher effect. Both 250 mg/kg and 500 mg/kg dose of E. officinalis and M. koenigii partially reversed cognitive decline in diabetic rats by day 30.Conclusions: 500 mg/kg p.o. dose of E. officinalis or M. koenigii has potential to reverse cognitive decline in diabetic patients.

Aqueous and ethanol extracts ofDracaena arborea(Wild) Link (Dracaenaceae) alleviate reproductive complications of diabetes mellitus in rats

Reproductive dysfunction is one of the most prevalent diabetes complications. Draceana arborea is known to enhance sexual function in diabetic rats, but the underlying mechanisms have not been thoroughly elucidated. This study examined the effects of D.arborea on some reproductive complications of diabetes in rats. Aqueous and ethanol (500 and 100mg/kg respectively) extracts of D.arborea, Sildenafil citrate (1.44mg/kg), trimethylamine-N-oxide (TMAO, 20mg/kg) and distilled water (10ml/kg) were orally administered for 28days to streptozotocin-induced diabetic rats. Glycaemia, body and reproductive organ masses, fertility parameters, total proteins, antioxidant enzymes activities, serum and testicular testosterone and the histology of the testes and epididymis were determined. Results revealed significant decreases in body and absolute and relative masses of testes, epididymis, seminal vesicles, prostate and vas deferens, fertility parameters, epididymal and testicular total proteins, serum and testicular testosterone levels as well as antioxidant enzymes activities. Interestingly, while having minor anti-hyperglycaemic effects, these abnormalities associated with testicular and epididymal alterations were alleviated by D.arborea especially the aqueous extract (500mg/kg). These outcomes provided evidence of the androgenic properties of D.arborea in diabetic rats, which could be useful for a better management of sexual dysfunctions in diabetic patients.

Intracavernosal Adeno-Associated Virus-Mediated S100A1 Gene Transfer Enhances Erectile Function in Diabetic Rats by Promoting Cavernous Angiogenesis via VEGF-A/VEGFR2 Signaling

IntroductionNovel therapeutic targets for diabetes-induced erectile dysfunction (DED) are urgently needed. Previous studies have proved that S100A1, a small Ca2+-binding protein, is a pluripotent regulator of cardiovascular pathophysiology. Its absence is associated with endothelial dysfunction, the central event linking cardiovascular changes in diabetes. However, the role of S100A1 in DED remains unknown. AimTo explore the effect and underlying mechanisms of S100A1 in restoring erectile function in type I diabetic rat model. MethodsDiabetes was induced by intraperitoneal injection of streptozotocin and then screened by apomorphine (APO) to confirm erectile dysfunction. Rats that met the criteria of penile erection were marked as APO-positive; otherwise, the result was APO-negative. In experiment 1, S100A1 gene expression alterations in the corpus cavernosum in moderate and established stages of DED were analyzed. In experiment 2, S100A1 and control GFP gene were delivered into the corpus cavernosum in APO-negative rats by adeno-associated virus (AAV) serotype 9. Erectile function was assessed at 4 weeks after gene therapy. Main Outcome MeasuresErectile response, histologic and molecular alterations. ResultsS100A1 protein was localized to the area surrounding the cavernosal sinusoids in the penis, and it was gradually downregulated synchronized with the progression of DED. Compared with an injection of AAV-GFP, a single injection of AAV-S100A1 significantly restored erectile function in diabetic rats. S100A1 overexpression significantly upregulated the expression of endogenous VEGF-A, promoted VEGFR2 internalization, and subsequently triggered the protein kinase B–endothelial nitric oxide synthase pathway in diabetic erectile tissues. Marked increases in nitric oxide and endothelial content were noted in AAV-S100A1-treated diabetic rats. Clinical ImplicationsLocal S100A1 overexpression may be an alternative therapy for DED and should be further investigated by future clinical studies. Strength & LimitationsThis is the first study demonstrating the angiogenic role of S100A1 in DED, but does not preclude the contribution of the effects of S100A1 in other tissues such as the neuronal tissue on the functional effects observed in erectile responses. ConclusionThe decreased expression of S100A1 during hyperglycemia might be important in the development of erectile dysfunction. S100A1 may play a potential role in restoring erectile function in rats with DED through modulating cavernous angiogenesis.Yu Z, Zhang Y, Tang Z, et al. Intracavernosal Adeno-Associated Virus-Mediated S100A1 Gene Transfer Enhances Erectile Function in Diabetic Rats by Promoting Cavernous Angiogenesis via VEGF-A/VEGFR2 Signaling. J Sex Med 2019;16:1344–1354.

Trimetazidine inhibits cardiac fibrosis by reducing reactive oxygen species and downregulating connective tissue growth factor in streptozotocin-induced diabetic rats.

Diabetes may affect myocardial fibrosis through oxidative stress. Trimetazidine (TMZ) is an anti-anginal agent. The present study aimed to determine the modulatory effect of TMZ on reactive oxygen species (ROS) and connective tissue growth factor (CTGF) expression and to evaluate the potential of TMZ to improve diastolic function in streptozotocin (STZ)-induced diabetic rats. After treating STZ-induced diabetic rats with TMZ for 16 weeks, a decrease in malondialdehyde levels, cardiac collagen volume fraction, left ventricular (LV) end-diastolic pressure and protein expression of collagen-I (Col I), Col III and CTGF compared with those in diabetic control rats was observed. In vitro, TMZ inhibited Col I, Col III and CTGF protein expression in cardiac fibroblasts treated with high glucose and decreased intracellular ROS generation and hydroxyproline content in the cell culture medium of cardiac fibroblasts. TMZ markedly improved cardiac fibrosis and diastolic function in diabetic rats. This effect was associated with a reduction in ROS production and CTGF expression in cardiac fibroblasts. The present study suggests that TMZ may be beneficial for protecting the hearts of diabetic patients.

Combined effects of arsenic exposure and diabetes on male reproductive functions.

It is known that exposure to either arsenic or hyperglycemia can induce male reproductive damages. However, their combined effects on male reproductive organs are still unclear. Therefore, the present study investigated morphological and functional parameters of the testis, epididymis, and spermatozoa in diabetic rats exposed to arsenate. Diabetes was induced in male rats by intraperitoneal streptozotocin injection. While a set of healthy and diabetic animals received saline solution (negative control and diabetes control, respectively), the other set received 10mg/L sodium arsenate (arsenic control and diabetes + arsenic groups, respectively) for 40days in drinking water. Testosterone concentration, daily sperm production, sperm counts in the testis and epididymis, and sperm parameters were evaluated in the groups. Moreover, testis and epididymis were subjected to antioxidant enzymes analysis, micromineral determination, and histopathological evaluation. Arsenate exposure reduced serum testosterone concentration in healthy animals and worsened this reduction in diabetic rats. In addition, the number of spermatozoa in testis and epididymis tissues, as well as the daily sperm production, was decreased in these groups. Sperm parameters such as motility, morphology, and integrity of acrosomal and plasma membranes were impaired in health animals exposed to arsenate. The combination of diabetes and arsenate, in turn, increased only the percentage of spermatozoa with abnormal morphology. Moreover, the proportion of arsenic increased in the testis and epididymis of both groups receiving arsenate. Its bioaccumulation in these organs caused an imbalance in antioxidant enzymes activities and mineral content in healthy animals, enhancing these changes in diabetic rats. Testicular pathologies occurred mainly in animals co-exposed to diabetes and arsenate. Our results indicate that arsenate exposure enhances several damages to male reproductive functions in diabetic rats, mainly by impairing testosterone levels and inducing nitrosative stress in testis and epididymis.

Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats.

Objective In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 μg/kg/day), high (0.1 μg/kg/day), and high (0.1 μg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 μg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

Oral administration of green tea Epigallocatechin-3-gallate reduces oxidative stress and enhances restoration of cardiac function in diabetic rats receiving autologous transplantation of adipose-derived stem cells

Background Cardio-dysfunction is one of the complications in patients with diabetes mellitus (DM). This paper aimed to investigate if oral administration of green tea Epigallocatechin-3-gallate (EGCG, E) and transplantation of adipose-derived stem cells (ADSC) show cross effects on the treatment of cardiomyopathy in rats with type 1 DM. Materials and methods Wistar male rats were divided into four groups (each group contained 8 animals) including sham, DM (diabetic group), DM + ADSC (DM group with ADSC treatment) and DM + ADSC + E (DM + ADSC group with oral administration of EGCG). Results Pathological parameters including hypertrophy, inflammation, and fibrosis were activated in DM group. By contrast, all parameters were significantly improved in treatment group (DM + ADSC group). In addition, improvement of pathological parameters in DM + ADSC + E was significantly better than DM + ADSC. Conclusion We found that EGCG can increase expression of survival marker in ADSC under high glucose environment and reduce serum oxidative stress in DM rats.

Impact of diabetes on male sexual function in streptozotocin-induced diabetic rats: Protective role of soluble epoxide hydrolase inhibitor

Diabetes-induced male sexual dysfunction is associated with endothelial dysfunction. Inhibition of soluble epoxide hydrolase (sEH) is known to improve endothelial function in diabetes. Therefore, we hypothesized that sEH inhibitor (sEHI), [trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid] / t-TUCB can restore the male sexual function in diabetic rat. After one week of administration of diabetogenic agent STZ (52 mg/kg i.p) injection, diabetic rats were treated with t-TUCB (0.1 and 0.3 mg/kg, p.o) or vehicle for 8 weeks. The sexual behaviour parameters of the animals were evaluated at the end of dosing period. The levels of testosterone and glucose in serum, and sperm were quantified. Effect of treatment on weight of reproductive organs and histopathology of penile tissue was evaluated. Diabetes had a negative effect on male sexual function, weight of sexual organs and production of sperm with a parallel decrease in the level of testosterone. The sEHI, t-TUCB, significantly preserved the sexual function and minimized an increase in the level of blood glucose in diabetic rats. It also prevented a decrease in the level of testosterone and sperm in diabetic rats, in comparison to diabetic control rats. Further, diabetes induced distortion of corpus cavernosum was attenuated by t-TUCB. Based on our findings, sEHI may delay the development of sexual dysfunction in diabetes.

Dibutyryl cAMP Enhances Cognitive Functions in Diabetic Rats by Increasing the Hippocampal Neurogenesis

Dibutyryl cyclic adenosine monophosphate (dBcAMP) is a cell‐permeable synthetic analog of cyclic adenosine monophosphate (cAMP) known to acts as an intracellular second messenger for neurotransmitters and hormones. dBcAMP enhances differentiation and survival of neurons from neuronal stem cells, differentiation of mesenchymal stromal cell into neurons and stimulates the differentiation of astrocytes and contribute to neuroprotection in neural tissue injury.Diabetes, a chronic metabolic disease has adverse effects on adult hippocampal neurogenesis and cognitive function. Even though, dBcAMP is used as a therapeutic agent in some disease models, it has not been used in diabetes. Present experiment was aimed to study the effects of dBcAMP on learning and memory and adult neurogenesis, in streptozotocin model of diabetic rats. Diabetes was induced in male Wistar rats (3 months old) by injecting streptozotocin (ip, 50mg/kg) into the peritoneal cavity. After confirming the diabetic condition (hyperglycemia) in these rats after 48hrs of STZ injection, they were grouped into diabetic (DI) and diabetic+dBcAMP (DI+dBcAMP groups. Age matched normal rats served as control group (C). DI+dBcAMP group were treated with dBcAMP (ip,10mg/kg) intraperitoneally for 10 days and C and DI groups were be treated with PBS for the same duration. After treatment, animals in all groups were subjected to learning and memory test in Morris water maze from day21 to day27 of the experiment to assess the cognitive function. After the behavioral test rats (n=6 in all groups) were sacrificed on day 30. Fresh hippocampal tissue were collected for ELISA (for BDNF, brain derived neurotrophic factor), and Western blot (for doublecortin, DCX) analysis. Rats (n=6 in all groups), were be perfused with 4% paraformaldehyde and hippocampi were collected for immunostaining (DCX). Number of DCX positive neurons were quantified in the hippocampal dentate gyrus. Data were analyzed by One/Two –way ANOVA, followed by Bonferroni's multiple comparison test. Results showed a significant memory deficit (decreased time spent and distance traveled in platform quadrant) in DI rats compared to C (p&lt;0.001, One way ANOVA), and memory was significantly increased in DI+ dBcAMP compared to DI group (p&lt;0.001). Analysis of number of DCX positive neurons in the dentate gyrus (neurogenesis) showed a significant decrease in neurogenesis in DI group compared to C group (p&lt;0.001, One‐way ANOVA) and it was significantly increased in DI+dBcAMP (p&lt;0.001, One‐way ANOVA). Western blot analysis for DCX showed significant increase in DI+ dBcAMP group (p&lt;0.01) and hence confirmed the DCX positive neuron count data. Analysis of BDNF levels in the hippocampus of the DI+dBcAMP was found to be significantly increased compared to DI group (p&lt;0.01). We conclude that dBcAMP enhances cognitive functions in diabetic rats by increasing the Hippocampal BDNF levels and hence enhanced neurogenesis. Thus dBcAMP may be a potential molecule to be considered in treatment of diabetic patients to prevent the cognitive deterioration.Support or Funding InformationCollege of Graduate Studies and Research Sector, Kuwait UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.