scholarly journals Effect of Aspirin on Mitochondrial Dysfunction and Stress in the Pancreas and Heart of Goto-Kakizaki Diabetic Rats

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 902
Author(s):  
Annie John ◽  
Layla Amiri ◽  
Jasmin Shafarin ◽  
Frank Christopher Howarth ◽  
Haider Raza
Keyword(s):  
Redox Homeostasis ◽  
Control Level ◽  
Diabetic Rats ◽  
Cytochrome P450 Enzyme ◽  
Gk Rats ◽  
Insulin Resistant ◽  
Mitochondrial Functions ◽  
Stress Dependent ◽  
Type 2 Diabetic

Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.

Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats

2011 ◽  
Vol 300 (4) ◽  
pp. H1174-H1181 ◽  
Author(s):  
Julia Grönros ◽  
Christian Jung ◽  
Jon O. Lundberg ◽  
Ruha Cerrato ◽  
Claes-Göran Östenson ◽  
...  
Keyword(s):  
Vascular Function ◽  
Wistar Rats ◽  
Diabetic Rats ◽  
Microvascular Function ◽  
Vascular Integrity ◽  
Gk Rats ◽  
Type 2 Diabetic ◽  
Coronary Microvascular Function

Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common substrate arginine, resulting in diminished production of NO. The aim of this study was to evaluate coronary microvascular function in type 2 diabetic Goto-Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA), l-arginine, and the NOS inhibitor NG-monomethyl -l-arginine (l-NMMA). GK rats had impaired CFVR compared with Wistar rats (1.31 ± 0.09 vs. 1.87 ± 0.05, P < 0.001). CFVR was restored by nor-NOHA treatment compared with vehicle in GK rats (1.71 ± 0.13 vs. 1.23 ± 0.12, P < 0.05) but remained unchanged in Wistar rats (1.88 ± 0.10 vs. 1.79 ± 0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine compared with vehicle. Arginase II expression was increased in the aorta and myocardium from GK rats compared with Wistar rats. Citrulline-to-ornithine and citrulline-to-arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats after nor-NOHA treatment, suggesting a shift of arginine utilization from arginase to NOS. In conclusion, coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability.

Zinc ions in beta-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallography

Apmis ◽  
2003 ◽  
Vol 111 (12) ◽  
pp. 1147-1154 ◽  
Author(s):  
L. G. SONDERGAARD ◽  
M. STOLTENBERG ◽  
A. FLYVBJERG ◽  
B. BROCK ◽  
O. SCHMITZ ◽  
...  
Keyword(s):  
Beta Cells ◽  
Diabetic Rats ◽  
Zinc Ions ◽  
Insulin Resistant ◽  
Type 2 Diabetic

scholarly journals Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

2011 ◽  
Vol 106 (5) ◽  
pp. 648-655 ◽  
Author(s):  
Jiejie Hao ◽  
Weili Shen ◽  
Lijuan Sun ◽  
Jiangang Long ◽  
Edward Sharman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Diabetic Rats ◽  
Plasma Nefa ◽  
Quinone Oxidoreductase ◽  
Gk Rats ◽  
Total Antioxidant ◽  
And Oxidative Stress ◽  
Type 2 Diabetic

Treatment with a combination of four nutrients, i.e. R-α-lipoic acid, acetyl-l-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto–Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.

scholarly journals Alteration of Pharmacokinetics of Grepafloxacin in Type 2 Diabetic Rats

2014 ◽  
Vol 17 (1) ◽  
pp. 25 ◽  
Author(s):  
Meguho Watanabe ◽  
Masaki Kobayashi ◽  
Jiro Ogura ◽  
Natsuko Takahashi ◽  
Hiroaki Yamaguchi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Expression Level ◽  
Glycoprotein P ◽  
Gk Rats ◽  
Diabetes Model ◽  
Secretory Transport ◽  
Type 2 Diabetic

Purpose. Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux transporters. Methods. We used Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes. Plasma concentration and intestinal, renal, and biliary clearance of GPFX were measured after intravenous and intraintestinal administration in Wistar and GK rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Results. We found a significant increase in the plasma concentrations of GPFX at 90, 120 and 240 minutes after intraintestinal administration in GK rats compared with the concentrations in Wistar rats but not after intravenous administration. The increase in plasma GPFX concentration was associated with reduction in jejunal clearance of GPFX caused by a decrease in secretory transport of GPFX. However, there was no correlation between the decrease in secretory transport of GPFX and P-gp expression level. Conclusion. Type 2 diabetic conditions alter P-gp function as well as expression level and correlate poorly with each other. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Study on the Effect of Cerium Oxide Nanocubes on Full-Thickness Cutaneous Wound Healing of Type 2 Diabetic Rats

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 643-P ◽  
Author(s):  
YANFEI HAN ◽  
LINDONG LI ◽  
YANJUN LIU ◽  
YOU WANG ◽  
CHUNHUA YAN ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cerium Oxide ◽  
Diabetic Rats ◽  
Cutaneous Wound Healing ◽  
Full Thickness ◽  
Cutaneous Wound ◽  
Type 2 Diabetic

Neuroprotection of Maslinic Acid, a Novel Glycogen Phos-phorylase Inhibitor, in Type 2 Diabetic Rats

2010 ◽  
Vol 8 (4) ◽  
pp. 293-297 ◽  
Author(s):  
Teng GUAN ◽  
Yi-Song QIAN ◽  
Meng-Hao HUANG ◽  
Long-Fei HUANG ◽  
Xu-Zhen TANG ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Maslinic Acid ◽  
Type 2 Diabetic

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

2020 ◽  
Vol 20 (3) ◽  
pp. 464-478 ◽  
Author(s):  
Yomna M. Yehya ◽  
Abdelaziz M. Hussein ◽  
Khaled Ezam ◽  
Elsayed A. Eid ◽  
Eman M. Ibrahim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiac Arrhythmias ◽  
Sympathetic Nerve ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Angiotensin System ◽  
Type 2 Dm ◽  
Type 2 Diabetic ◽  
Diabetes Induction

Objectives:: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Methods:: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). Results:: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. Conclusions:: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

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