scholarly journals Liraglutide protects cardiac function in diabetic rats through the PPARα pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cardiac Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Serum Adiponectin ◽  
Diabetic Rat ◽  
Lv Function ◽  
High Dose ◽  
And Oxidative Stress

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 (GLP-1) analog, liraglutide, would attenuate cardiac dysfunction in diabetic rats. A total of 24 Sprague–Dawley (SD) rats were divided into two groups fed either a normal diet (normal, n=6) or a high-fat diet (HFD, n=18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into three subgroups receiving vehicle (diabetic, n=6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n=6), or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n=6). Metabolic parameters, systolic blood pressure (SBP), heart rate (HR), left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, nitric oxide (NO). Liraglutide improved insulin resistance, serum adiponectin, NO, HR, and LV function and reduced blood triglyceride (TG), total cholesterol (TC) levels, and oxidative stress. Moreover, liraglutide increased heart nuclear receptor subfamily 1, group H, member 3 (Nr1h3), peroxisome proliferator activated receptor (Ppar) α (Pparα), and Srebp expression and reduced diacylglycerol O-acyltransferase 1 (Dgat) and angiopoietin-like 3 (Angptl3) expression. Liraglutide prevented cardiac dysfunction by activating the PPARα pathway to inhibit Dgat expression and oxidative stress in diabetic rats.

The aging-induced hyperexcretion of glucose-dependent insulinotropic peptide is essential for the healthy cardiac remodeling by prevention of cardiac ceramide accumulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Kureishi Bando ◽  
Y.R Remina ◽  
T.K Kamihara ◽  
K.N Nishimura ◽  
T.M Murohara
Keyword(s):  
Oxidative Stress ◽  
Ketone Bodies ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lv Function ◽  
Cardiac Aging ◽  
Normal Left Ventricular ◽  
Insulinotropic Peptide ◽  
Ceramide Accumulation ◽  
And Oxidative Stress

Abstract Background Glucose-dependent insulinotropic peptide (GIP) is incretin hormone that is emerged as an important regulator of lipid metabolism. Fat intake induces hypersecretion of GIP that is involved in obesity and ectopic fat accumulation. Aging is another stimulant of GIP hypersecretion, which is suggested as a cause of “sarcopenic obesity in elderly”. In heart, aging is the known risk factor of HFpEF, of which typical characteristics is pathological cardiac hypertrophy induced by unknown cause(s). It remained uncertain whether any ectopic fat accumulation, such as cardiac steatosis may cause the aging-induced cardiac hypertrophy. Ceramide is one of the lipid metabolites that involves in apoptosis, inflammation, and stress responses, which are among the pathogenic components of heart failure. However, it remained unclear whether the ceramide may play any pathophysiological role in cardiac aging. Purpose We thus hypothesized whether cardiac aging may alter cardiac lipid metabolism and the GIP may play a regulatory role in the cardiac aging via modulating cardiac steatosis, particularly ceramide. Methods Mouse model of GIPR deficiency (GIPR-KO) was employed and cardiac evaluation of GIPR-KO and the age-matched wild type mice were performed. Results Aging (50w/o) induced GIP hypersecretion in control mice and their body and heart weight were 50% increased as compared to younger counterpart (10w/o). In contrast, the aging-induced increase rate in body and heart weight of GIPR-KO was significantly lower (22%). Aging also increased the circulating ketone bodies with increase in FGF21 expression in heart and, notably, there was no pathological increase in cardiac ceremide and oxidative stress with normal left-ventricular (LV) function (LVEF=82.2±1.8). In contrast, GIPR-KO exhibited pathological increase in cardiac ceramide without the elevation of the circulating ketone bodies. The younger GIPR-KO (10 w/o) exhibited normal left-ventricular (LV) function, however, the older mice (50 w/o) exhibited systolic LV dysfunction (LVEF=55.8±8.5) with increase in cardiac apoptosis and oxidative stress. Cardiac ceramide accumulation was increased in the aged normal mice, which was significantly higher in the aged GIPR-KO. Furthermore, GIPR-KO exhibited increase in cardiac fibrosis and oxidative stress, which were absent in the aged normal counterpart. Conclusion Aging increased circulating GIP level the leads to compensatory rise in the circulating ketone bodies without pathological increase in cardiac ceremide and related oxidative stress in heart. Loss of GIP signaling caused pathological increase in cardiac ceramide, leading to the aging-induced progression of systolic left-ventricular dysfunction. Collectively, we conclude that the aging-induced GIP hyperexcretion is essential for the aging-induced healthy cardiac remodeling by augmenting compensatory ketone body elevation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKEN-HI

scholarly journals Alterations in Energy Metabolism, Mitochondrial Function and Redox Homeostasis in GK Diabetic Rat Tissues Treated with Aspirin

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 104
Author(s):  
Annie John ◽  
Layla Amiri ◽  
Jasmin Shafarin ◽  
Saeed Tariq ◽  
Ernest Adeghate ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Redox Homeostasis ◽  
Diabetic Rats ◽  
Endocrine Function ◽  
Diabetic Rat ◽  
Rat Tissues ◽  
Gk Rats ◽  
And Oxidative Stress

Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated the mechanism of action of aspirin in maintaining mitochondrial bioenergetics and redox metabolism in the liver and kidneys of GK rats. Aspirin reduced the production of reactive oxygen species (ROS) and oxidative stress-induced changes in GSH metabolism. Aspirin treatment also improved mitochondrial respiratory function and energy metabolism, in addition to regulating the expression of cell signaling proteins that were altered in diabetic animals. Ultrastructural electron microscopy studies revealed decreased accumulation of glycogen in the liver of aspirin-treated diabetic rats. Hypertrophic podocytes with irregular fusion of foot processes in the renal glomerulus and detached microvilli, condensed nuclei and degenerated mitochondria observed in the proximal convoluted tubules of GK rats were partially restored by aspirin. These results provide additional evidence to support our previous observation of moderation of diabetic complications by aspirin treatment in GK rats and may have implications for cautious use of aspirin in the therapeutic management of diabetes.

scholarly journals Curcumin and Its Analog Alleviate Diabetes-induced Damages by Regulating Inflammation and Oxidative Stress in Brain of Diabetic Rats​

2020 ◽  
Author(s):  
Chengfeng Miao ◽  
Hanbin Chen ◽  
Yulian Li ◽  
Ying Guo ◽  
Feifei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Western Blot ◽  
Diabetic Rats ◽  
High Dose ◽  
Diabetic Encephalopathy ◽  
Sprague Dawley ◽  
The Brain ◽  
And Oxidative Stress ◽  
Myelin Staining

Abstract Background: Diabetic encephalopathy is a severe diabetes complication with cognitive dysfunction and neuropsychiatric disability. The mechanisms underlying diabetic encephalopathy is believed to be relevant with oxidative stress, vascular amylin deposition, immune receptors, inflammation, etc. This study wanted to evaluate the ability of curcumin and its analog A13 to alleviate oxidative stress and inflammation in diabetes-induced damages in brain.Methods: Sixty adult male Sprague-Dawley rats were divided into 5 groups: normal control (NC) group, diabetes mellitus (DM) group, curcumin-treated diabetes mellitus (CUR) group, high dose of A13-treated diabetes mellitus (HA) group, low dose of A13-treated diabetes mellitus (LA) group. Activation of the nuclear factor kappa-B (NF-κB p65) pathway was detected by RT-qPCR, immunohistochemical (IHC) staining and Western blot; oxidative stress was detected by biochemical detection kit; brain tissue sections were stained with hematoxylin–eosin (HE) staining and Myelin staining. Results: RT-qPCR, IHC staining and Western blot showed that curcumin and A13 treatment could inhibit the NF-κB p65 pathway. Curcumin and A13 increased the activity of superoxide dismutase and decreased the malondialdehyde level in the brain of diabetic rats. Furthermore, HE staining and Myelin staining demonstrated that the histological lesions of the brain in diabetic rats could be significantly ameliorated by curcumin and A13.Conclusion: Curcumin analog A13 could alleviate the damages in the brain of diabetes rats by regulating the pathways of inflammation and oxidative stress. A13 may be a new potential therapeutic agent for diabetic encephalopathy.

scholarly journals Effects of Metformin in Combination with a Herbal Capsule (Glucoblock) on Insulin Resistance and Oxidative Stress Index in Type 2 Diabetic Rats

2021 ◽  
pp. 18-25
Author(s):  
Ojoye N. Briggs ◽  
Kemzi N. Elechi-amadi ◽  
Justice C. Ohaka ◽  
Edna O. Nwachuku ◽  
Bartimaeus S. Ebirien-agana
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Diabetic Control ◽  
Negative Control ◽  
Diabetic Rats ◽  
Stress Index ◽  
Control Group ◽  
Oxidative Stress Index ◽  
Treatment Groups ◽  
And Oxidative Stress

Aim: This study evaluated the effects of metformin in combination with a herbal capsule (glucoblock) on insulin resistance and oxidative stress index in type 2 diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis on the herbal capsule was done using classical methods. Results: The results revealed the presence of alkaloids (100.31μg/mg), flavonoids (131.45μg/mg), cardiac glycosides (55.93μg/mg) and saponins (61.47μg/mg) in the herbal drug glucoblock. The results showed significantly lower FPG levels in the treatment groups when compared to the diabetic control. Group 3 administered metformin had significantly higher FPG levels compared to the negative control. Group 4 administered the herbal drug glucoblock and group 5 administered a combination of metformin and glucoblock, showed no significant differences in FPG levels when compared to the negative control. The diabetic control had significantly higher FPI levels compared to the negative control and treatment groups. The treatment groups showed no significant differences in FPI levels when compared to the negative control. HOMA-IR was significantly higher in the diabetic control compared to the negative control and treatment groups. Also, HOMA-IR values in the treatment groups showed no significant difference compared to the negative control except for group 3 (metformin), that was significantly higher than the negative control. SOD was significantly lower in the diabetic control, compared to the negative control and treatment groups. There were no significant differences in SOD levels in the treatment groups compared to the negative control. TOS levels in the negative control group and treatment groups were significantly lower, compared to the diabetic control. TAS was significantly lower in the diabetic control and treatment groups compared to the negative control. OSI in the diabetic control was significantly higher, compared to the negative control and treatment groups. Also, the treatment groups had significantly higher OSI compared to the negative control. Conclusion: High fat diet and streptozotocin induction produced significant insulin resistance and oxidative stress in the diabetic rats. Glucoblock was more effective in reducing insulin resistance compared to metformin. The combination showed synergistic drug-herb reaction as glucoblock potentiated the actions of metformin. Both showed antioxidant potential but were not effective in lowering oxidative stress to normal levels. There is need to incorporate antioxidant therapy in the treatment protocol for diabetes mellitus.

scholarly journals The Effects of the Melatonin Treatment on the Oxidative Stress and Apoptosis in Diabetic Eye and Brain

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Tuğba Gürpınar ◽  
Nuran Ekerbiçer ◽  
Nazan Uysal ◽  
Turgay Barut ◽  
Figen Tarakçı ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Histopathological Changes ◽  
Melatonin Treatment ◽  
Adult Rats ◽  
Significant Difference ◽  
Immunohistochemical Methods ◽  
And Oxidative Stress

Oxidative stress plays an important role in the development of complications in diabetes mellitus. Antioxidant therapy has been thought to decrease oxidative stress. The objective of the present study was to explore the effects of melatonin (MLT) on oxidative stress in diabetic rat eye and brain tissue by using immunohistochemical methods. Diabetes was induced by streptozotocin, (STZ, 55 mg/kg/i.p) in adult rats. MLT was given 10 mg/kg/i.p once a day for 2 weeks beginning from the sixth week. Six weeks later, rats were divided into three groups: control (CR), STZ-induced diabetic (STZ), and STZ-induced diabetic group received melatonin (STZ+MLT). Although no significant difference was observed with respect to antioxidant status, NOS activity tended to be higher in the untreated diabetic rats than in the treated rats. It was observed that MLT treatment improved the histopathological changes including apoptosis and oxidative stress in brain and eye in diabetic rat.

scholarly journals Testosterone deprivation accelerates cardiac dysfunction in obese male rats

2016 ◽  
Vol 229 (3) ◽  
pp. 209-220 ◽  
Author(s):  
Wanpitak Pongkan ◽  
Hiranya Pintana ◽  
Sivaporn Sivasinprasasn ◽  
Thidarat Jaiwongkam ◽  
Siriporn C Chattipakorn ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Normal Diet ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Lv Function ◽  
Insulin Resistant ◽  
Aging Men

Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats.

scholarly journals Sodium-Glucose Cotransporter Inhibition Prevents Oxidative Stress in the Kidney of Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Horacio Osorio ◽  
Israel Coronel ◽  
Abraham Arellano ◽  
Ursino Pacheco ◽  
Rocío Bautista ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subcutaneous Administration ◽  
Immunohistochemical Analysis ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Sodium Glucose Cotransporter ◽  
Lower Body Weight ◽  
Sglt2 Inhibition ◽  
Streptozotocin Induced Diabetes ◽  
And Oxidative Stress

The hyperglycemia triggers several chronic diabetic complications mediated by increased oxidative stress that eventually causes diabetic nephropathy. The aim of this study was to examine if the sodium-glucose cotransporter (SGLT2) inhibition prevents the oxidative stress in the kidney of diabetic rats.Methods. The diabetic rat model was established by intraperitoneal injection of streptozotocin (50 mg/kg). The inhibition of SGLT2 was induced by daily subcutaneous administration of phlorizin (0.4 g/kg). Oxidative stress was assessed by catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities and by immunohistochemical analysis of 3-nitrotyrosine (3-NT).Results. Streptozotocin-induced diabetes caused hyperglycemia and lower body weight. The CAT activity decreased in cortex and medulla from diabetic rats; in contrast, the GPx activity increased. Furthermore the 3-NT staining of kidney from diabetic rats increased compared to control rats. The inhibition of SGLT2 decreased hyperglycemia. However, significant diuresis and glucosuria remain in diabetic rats. The phlorizin treatment restores the CAT and GPX activities and decreases 3-NT staining.Conclusion. The inhibition of SGLT2 by phlorizin prevents the hyperglycemia and oxidative stress in kidney of diabetic rats, suggesting a prooxidative mechanism related to SGLT2 activity.

scholarly journals Anethum graveolens L‎. Alleviates Sperm ‎Damage by Limiting Oxidative Stress ‎and Insulin ‎Resistance ‎in ‎Diabetic Rats ‎

2020 ◽  
Vol 14 (1) ◽  
pp. 35-44
Author(s):  
Ebrahim Abbasi-Oshaghi ◽  
Iraj Khodadadi ◽  
Fatemeh Mirzaei ◽  
Mehrdad Ahmadi ◽  
Heidar Tayebinia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Morphological Changes ◽  
Diabetic Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Anethum Graveolens ◽  
Sod Activity ◽  
Histological Changes ◽  
Anti Oxidant

Background: It has been reported that diabetes is associated with sperm ‎damage and infertility. Objective: The purpose of this experiment was to survey the effect of Anethum graveolens L. (Dill) powder on sperm profiles, oxidative stress, insulin resistance, and histological changes in male diabetic rats. Methods: Male rats were randomly divided into 6 groups (n=7); group 1: normal rats, 2: normal rats + 100mg/kg Dill, 3: normal rats + 300mg/kg Dill, 4: diabetic rats, 5: diabetic rats + 100mg/kg Dill, and 6: diabetic rats + 300mg/kg Dill. After 2 months of treatments, the sperm profile, anti-oxidant activity, superoxide dismutase (SOD) activity, and malondialdehyde were measured. The histopathology of testis was evaluated. Hormonal changes and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Results: Total anti-oxidant and SOD activity in diabetic rats significantly decreased, while MDA concentration was significantly increased in the testis and pancreas of diabetic rats compared with control. However, the use of Dill significantly normalized these profiles. The treatment of diabetic rats with Dill changed the sperm parameters. The levels of testosterone, FSH, and LH in diabetic rats were significantly reduced, but the treatment with Dill did not alter the level of these hormones. Dill also significantly normalized testis morphological changes, insulin resistance, and inflammation. Conclusion: The use of Dill normalized oxidative stress, inflammation, and insulin resistance in diabetic rats that correlated with sperm profile and testis histological changes. The treatment of diabetic rat models with Dill did not show harmful effects on sperm profiles.

scholarly journals Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats

2017 ◽  
Vol 232 (2) ◽  
pp. 189-204 ◽  
Author(s):  
Pongpan Tanajak ◽  
Hiranya Pintana ◽  
Natthaphat Siri-Angkul ◽  
Juthamas Khamseekaew ◽  
Nattayaporn Apaijai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Metabolic Regulation ◽  
Left Ventricular ◽  
Lv Function ◽  
Insulin Resistant

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats.

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