scholarly journals Liraglutide Preserves Intracellular Calcium Handling in Isolated Murine Myocytes Exposed to Oxidative Stress

2017 ◽  
pp. 889-895 ◽  
Author(s):  
S. PALEE ◽  
S. C. CHATTIPAKORN ◽  
N. CHATTIPAKORN
Keyword(s):  
Oxidative Stress ◽  
Decay Rate ◽  
Intracellular Calcium ◽  
Wistar Rats ◽  
Calcium Handling ◽  
Isolated Cardiomyocytes ◽  
Before And After ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca2+) overload. Glucagon-Like Peptide-1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca2+ regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 µM) applied before or after hydrogen peroxide (H2O2, 50 µM) treatment on intracellular Ca2+ regulation in isolated cardiomyocytes. We hypothesized that liraglutide can attenuate intracellular Ca2+ overload in cardiomyocytes under H2O2-induced cardiomyocyte injury. Cardiomyocytes were isolated from the hearts of male Wistar rats. Isolated cardiomyocytes were loaded with Fura-2/AM and fluorescence intensity was recorded. Intracellular Ca2+ transient decay rate, intracellular Ca2+ transient amplitude and intracellular diastolic Ca2+ levels were recorded before and after treatment with liraglutide. In H2O2 induced severe oxidative stressed cardiomyocytes (which mimic cardiac I/R) injury, liraglutide given prior to or after H2O2 administration effectively increased both intracellular Ca2+ transient amplitude and intracellular Ca2+ transient decay rate, without altering the intracellular diastolic Ca2+ level. Liraglutide attenuated intracellular Ca2+ overload in H2O2-induced cardiomyocyte injury and may be responsible for cardioprotection during cardiac I/R injury by preserving physiological levels of calcium handling during the systolic and diastolic phases of myocyte activation.

scholarly journals Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats

2020 ◽  
Vol 14 ◽  
Author(s):  
Vincent N. Marty ◽  
Mehdi Farokhnia ◽  
Joseph J. Munier ◽  
Yatendra Mulpuri ◽  
Lorenzo Leggio ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Alcohol Intake ◽  
Ethanol Intake ◽  
Addictive Behaviors ◽  
Gut Hormone ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Alcohol Seeking

Alcohol use disorder (AUD) is a chronic relapsing condition characterized by compulsive alcohol-seeking behaviors, with serious detrimental health consequences. Despite high prevalence and societal burden, available approved medications to treat AUD are limited in number and efficacy, highlighting a critical need for more and novel pharmacotherapies. Glucagon-like peptide-1 (GLP-1) is a gut hormone and neuropeptide involved in the regulation of food intake and glucose metabolism via GLP-1 receptors (GLP-1Rs). GLP-1 analogs are approved for clinical use for diabetes and obesity. Recently, the GLP-1 system has been shown to play a role in the neurobiology of addictive behaviors, including alcohol seeking and consumption. Here we investigated the effects of different pharmacological manipulations of the GLP-1 system on escalated alcohol intake and preference in male Wistar rats exposed to intermittent access 2-bottle choice of 10% ethanol or water. Administration of AR231453 and APD668, two different agonists of G-protein receptor 119, whose activation increases GLP-1 release from intestinal L-cells, did not affect voluntary ethanol intake. By contrast, injections of either liraglutide or semaglutide, two long-acting GLP-1 analogs, potently decreased ethanol intake. These effects, however, were transient, lasting no longer than 48 h. Semaglutide, but not liraglutide, also reduced ethanol preference on the day of injection. As expected, both analogs induced a reduction in body weight. Co-administration of exendin 9-39, a GLP-1R antagonist, did not prevent liraglutide- or semaglutide-induced effects in this study. Injection of exendin 9-39 alone, or blockade of dipeptidyl peptidase-4, an enzyme responsible for GLP-1 degradation, via injection of sitagliptin, did not affect ethanol intake or preference. Our findings suggest that among medications targeting the GLP-1 system, GLP-1 analogs may represent novel and promising pharmacological tools for AUD treatment.

Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats

2020 ◽  
pp. 1-13
Author(s):  
Jukkrapong Pinyo ◽  
Hiroshi Hara ◽  
Tohru Hira
Keyword(s):  
Wistar Rats ◽  
Control Diet ◽  
Postprandial Glucose ◽  
Diabetic Rats ◽  
Gk Rats ◽  
Obesity And Diabetes ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

Abstract Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.

scholarly journals NOX Inhibition Improves β Adrenergic-Stimulated Contractility and Intracellular Calcium Handling in the Aged Heart

2018 ◽  
Author(s):  
Alvaro Valdés ◽  
Guillermo Barrios ◽  
Nikol Ponce ◽  
Raul A Dulce ◽  
Daniel R Gonzalez
Keyword(s):  
Oxidative Stress ◽  
Intracellular Calcium ◽  
Negative Impact ◽  
Calcium Handling ◽  
Isolated Cardiomyocytes ◽  
Beta Adrenergic ◽  
Dependent Effect ◽  
Isolated Hearts ◽  
Nox Inhibitors ◽  
Isolated Cardiac Myocytes

Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart, [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. Contractility was evaluated isolated hearts, challenged with isoproterenol. To assess [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced in aged myocytes (p < 0.05), and further reduced by apocynin. Finally SERCA levels but not phospholamban were reduced in aged hearts (p < 0.05). In conclusion, β-adrenergic‒induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca2+ handling proteins and myofilaments.

scholarly journals The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suvanjaa Sivalingam ◽  
Emil List Larsen ◽  
Daniel H. van Raalte ◽  
Marcel H. A. Muskiet ◽  
Mark M. Smits ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Nucleic Acid ◽  
Urinary Excretion ◽  
Post Hoc Analysis ◽  
Significant Difference ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Post Hoc

AbstractGlucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

scholarly journals Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Redox Homeostasis ◽  
Brain State ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

Aortic-banding induces myocardial oxidative stress and changes in concentration and activity of antioxidants in male Wistar rats

Life Sciences ◽  
2006 ◽  
Vol 79 (23) ◽  
pp. 2187-2193 ◽  
Author(s):  
Maria H.V.M. Jacob ◽  
Mauro R.N. Pontes ◽  
Alex S.R. Araújo ◽  
Jaqueline Barp ◽  
Maria C. Irigoyen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Aortic Banding ◽  
Myocardial Oxidative Stress ◽  
Male Wistar Rats
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