Protective Effects Of Exenatide Research Articles

Testicular cytoprotective effect of glucagon like peptide-1 in diabetic rats involves inhibition of apoptosis, endoplasmic reticulum stress and activation of autophagy.

This study aimed to explore the possible cytoprotective effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the testicles of diabetic rats. Exenatide has numerous advantageous properties in addition to its hypoglycemic effect. However, its impact on testicular tissue in diabetes needs more clarification. Therefore, rats were divided into control, exenatide-treated, diabetic and exenatide-treated diabetic groups. Blood glucose and serum levels of insulin, testosterone, pituitary gonadotropins and kisspeptin-1 were measured. Real-time PCR for beclin-1, p62, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), were estimated in testicular tissue in addition to markers of oxidative stress, inflammation, and endoplasmic reticulum stress. Also, immuno-expression of protein P53, nuclear erythroid factor2 (Nrf2) and vimentin was conducted. Exenatide was able to attenuate diabetic toxic changes and enhance autophagy in testicular tissue. These results indicate the protective effect of exenatide against diabetic testicular dysfunction.

Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model.

Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2mg/kg) injected intraperitoneally 30min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180min. Blood glucose level was measured in the study groups 30min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.

Protective effect of exenatide (glucagon-like peptide-1 receptor agonist) on renal ischemia–reperfusion injury in diabetic rats

Protective effect of exenatide (glucagon-like peptide-1 receptor agonist) on renal ischemia–reperfusion injury in diabetic rats

Protective effect of exenatide (glucagon-like peptide-1 receptor agonist) on renal ischemia–reperfusion injury in diabetic rats

Aim Diabetes mellitus (DM), especially type 2, is a major health problem, and diabetic nephropathy is the main cause of end-stage renal disease. Renal ischemia–reperfusion (I/R) injury is common in diabetic patients. Recent studies reported increased vulnerability of kidneys to I/R injury in diabetic rats. In view of the reported efficacy of glucagon-like peptide-1 (GLP-1) on I/R injury, this study was designed to assess the effect of exenatide (GLP-1) on renal I/R in type 2 DM. Materials and methods Type 2 DM in rats was induced by administration of nicotinamide (110 mg/kg, intraperitoneal), 15 min before a single dose of streptozotocin (45 mg/kg, intraperitoneal). Renal I/R was performed in both diabetic and normal rats. The protocol comprised ischemia for 30 min followed by reperfusion for 24 h aynd a treatment period with exenatide 2 weeks before induction of ischemia. Results Renal I/R in diabetic rats induced marked renal dysfunction associated with a significant increase in malondialdehyde, nitric oxide, and tumor necrosis factor α levels. Antioxidant enzymes such as reduced glutathione and superoxide dismutase were significantly reduced. Exenatide treatment significantly normalized these biochemical parameters compared with diabetic I/R rats. Conclusion In conclusion, exenatide protects renal I/R injury in type 2 DM. These findings have major implication in the treatment of ischemic injury that is prone to develop in DM.

Exenatide protects against hypoxia/reoxygenation-induced apoptosis by improving mitochondrial function in H9c2 cells

Glucagon-like peptide-1 (GLP-1) analogues might exert the cardioprotective effects via attenuating apoptosis. This study aimed to determine the protective effects and mechanism of exenatide, a GLP-1 analogue, on cardiomyocyte apoptosis using an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. 200 nM exenatide pretreatment significantly reduced apoptosis measured by flow cytometry. To further study the antiapoptotic mechanism of exenatide, we used flow cytometry in combination with laser confocal microscopy to determine the interaction between exenatide and the process of mitochondria-mediated apoptosis. We found that exenatide pretreatment reduced the intracellular reactive oxygen species (ROS) levels and decreased the mitochondrial calcium overload caused by H/R. Furthermore, an increase of total superoxide dismutase (T-SOD) levels, a decrease of malondialdehyde (MDA) levels, a preservation of mitochondrial membrane potential (ΔΨm), a reduction of cytochrome-c release, a decline of cleaved caspase-3 expression, and caspase-3 activation were observed in exenatide-pretreated cultures. These results suggest that exenatide exerts a protective effect on preventing against H/R-induced apoptosis. Importantly, the protective effects of exenatide may be attributed to its role in improving mitochondrial function in H9c2 cells subjected to H/R.

Protection of exenatide for retinal ganglion cells with different glucose concentrations

Exendin-4 is a peptide resembling glucagon-like peptide-1 (GLP-1), which has protective effects on nerve cells. However, the effects of Exendin-4 on retinal ganglion cells (RGC) are still under clear. The purpose of the present study is to demonstrate that exenatide prevents high- or low-glucose-induced retinal ganglion cell impairment. We observed the expression of GLP-1R in RGC-5 cells by immunofluorescence and Western blot. To investigate the effect of exenatide on RGC-5 cells incubated different glucose concentrations, CCK-8 measured the survival rates and electron microscopy detected cellular injury. The expression levels of Bcl-2 and Bax were analyzed by immunocytochemistry and Western blot. Exenatide protects RGC-5 from high- or low-glucose-induced cellular injury and the optimum concentration was 0.5μg/ml. Exenatide can inhibit high- or low-glucose-induced mitochondrial changes. Exenatide protects RGC-5 from high- or low-glucose-induced Bax increased and Bcl-2 decreased. Furthermore, the protective effect of exenatide could be inhibited by Exendin (9-39). These findings indicate that exenatide shows a neuroprotective effect for different glucose concentrations-induced RGC-5 cells injury. Exenatide could protect RGC-5 cells from degeneration or death, which may protect retinal function and have a potential value for patients with diabetic retinopathy.

Exenatide prevents high-glucose-induced damage of retinal ganglion cells through a mitochondrial mechanism

Exenatide (exendin-4 analogue) is widely used in clinics and shows a neuroprotective effect. The main objectives of the present study were to prove that retinal ganglion cells (RGC-5) express GLP-1R, to ascertain whether exenatide prevents a high-glucose-induced RGC-5 impairment, to determine the appropriate concentration of exenatide to protect RGC-5 cells, and to explore the neuroprotective mechanisms of exenatide. Immunofluorescence and Western blot analyses demonstrated that RGC-5 cells express GLP-1R. We incubated RGC-5 cells with 25mM glucose prior to incubation with either 25mM glucose, 55mM glucose (high), high glucose plus exenatide or high glucose plus a GLP-1R antagonist. The survival rates of the cells were measured by CCK-8, and cellular injury was detected by electron microscopy. There were statistical differences between the high-glucose group and the control group (P<0.05). Exenatide improved the survival rate of the cells and suppressed changes in the mitochondrial morphology. The optimum concentration of exenatide to protect the RGC-5 cells from high-glucose-induced RGC injury was 0.5μg/ml, and this protective effect could be inhibited by exendin (9–39). To further study the mechanism underlying the beneficial effects of exenatide, the expression levels of cytochrome c, Bcl-2, Bax and caspase-3 were analysed by Western blot. The present study showed that treatment with exenatide significantly inhibited cytochrome c release and decreased the intracellular expression levels of Bax and caspase-3, whereas Bcl-2 was increased (P<0.05). These results suggested that GLP-1R activation can inhibit the cellular damage that is induced by high glucose. A mitochondrial mechanism might play a key role in the protective effect of exenatide on the RGC-5 cells, and exenatide might be beneficial for patients with diabetic retinopathy.