Abstract 313: Nonionic Acid is a Target Metabolite of Diabetic Microvasculopathy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yasuko K Bando ◽  
Haruya Kawase ◽  
Kazuyuki Nishimura ◽  
Akio Monji ◽  
Toyoaki Murohara
Keyword(s):  
Diabetic Microangiopathy ◽  
Tube Length ◽  
Nonanoic Acid ◽  
Branch Points ◽  
Metabolome Analysis ◽  
Whole Heart ◽  
The Impact ◽  
Type 2 Diabetic

Aim: The purpose of this study is to screen the target metabolites of diabetic microangiopathy in heart by use of whole heart metabolome analysis. Methods: Diet-induced type 2 diabetic mouse were divided into two groups; control and those treated with diabetic remedy GLP-1 receptor agonist Ex-4 for 5 weeks. Mice were euthanized and analyzed at the age of 16 week-old. Results: The capillary density of the T2DM was reduced as compared to those non-diabetic counterparts, which was restored by Ex4 treatment. Changes in angiogenic signals detected by immunoblotting analysis revealed that the phosphorylation levels of eNOS and AMPK were elevated by Ex-4, but those Akt remained unchanged. Tube formation assay revealed that Ex-4 increased tube length and branch points in HUVECs. Consistently with the trend that was observed in vivo experiment, AMPK and eNOS phosphorylation levels were enhanced by Ex4 without affecting Akt phosphorylation. To screen the candidate metabolites that is responsible for the diabetic microvasculopathy in GLP-1-dependent fashion, we performed metabolome analysis by using the whole heart of each mouse. The hierarchical cluster analysis revealed that nonanoic acid (NNA) was the only metabolite that increased in type 2 diabetic mice with concomitant decline by Ex-4 treatment. We next examined the impact of nonanoic acid on in vitro angiogenesis and found that NNA suppressed tube length and branch points in HUVECs in a dose-dependent fashion. Interestingly, NNA canceled eNOS and AMPK phosphorylation that was enhanced by Ex4. Conclusion: GLP-1 ameliorated diabetic microvasculopathy via the AMPK and eNOS axis. NNA is presumably one of the novel anti-angiogenic metabolites that causes diabetic microangiopathy.

In vitro nutrition properties of whole Tartary buckwheat straight noodles and its amelioration on type 2 diabetic rats

2021 ◽  
pp. 101525
Author(s):  
Xiaojiang Wu ◽  
Guiming Fu ◽  
Ziwen Xu ◽  
Biao Dong ◽  
Ruyi Li ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Tartary Buckwheat ◽  
Type 2 Diabetic

scholarly journals Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans 

2021 ◽  
Author(s):  
Heera Ram ◽  
Pramod Kumar ◽  
Ashok Purohit ◽  
Priya Kashyap ◽  
Suresh Kumar ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Model Assessment ◽  
Fruit Extract ◽  
Protein Ligands ◽  
Homeostatic Model Assessment ◽  
Docking Protein ◽  
Type 2 Diabetic

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay as well as significantly inhibit serum DPP-4 levels. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

Improvements in HOMA Indices and Pancreatic Endocrinal Tissues in Type -2 Diabetic Rats by DPP-4 Inhibition and Antioxidant Potential of an Ethanol Fruit Extract of Withania Coagulans

2020 ◽  
Author(s):  
Heera Ram ◽  
Pramod Kumar ◽  
Ashok Purohit ◽  
Priya Kashyap ◽  
Suresh Kumar ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Model Assessment ◽  
Fruit Extract ◽  
Withania Coagulans ◽  
Homeostatic Model Assessment ◽  
Docking Protein ◽  
Type 2 Diabetic

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of phytochemicals of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

Myricetin May Provide Protection against Oxidative Stress in Type 2 Diabetic Erythrocytes

2009 ◽  
Vol 64 (9-10) ◽  
pp. 626-630 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Neetu Mishra ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Biological Effects ◽  
Protein Carbonyl ◽  
In Vivo Studies ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Protein Carbonyl Content ◽  
Type 2 Diabetic

Oxidative stress is believed to be a major contributing factor in the development of late complications of diabetes. Many in vitro and in vivo studies have demonstrated that several parameters of red blood cell function and integrity are negatively affected by increased oxidative stress. Plant polyphenols are reported to exert many biological effects due to their antioxidant property. The present study was undertaken to evaluate the antioxidant effect of myricetin on markers of oxidative stress in erythrocytes from type 2 diabetic patients. The study was carried out on blood samples obtained from 23 type 2 diabetic patients and 23 age-matched control subjects. Erythrocytes were subjected to in vitro oxidative stress by incubating with 10-5 M tert-butyl hydroperoxide (t-BHP). Erythrocyte membrane lipid peroxidation and protein oxidation were measured in terms of malondialdehyde (MDA) and protein carbonyl group levels. The results showed an elevated MDA and protein carbonyl content in diabetic erythrocytes which were further increased after incubation with t-BHP. Myricetin at micromolar concentration significantly (p < 0.01) protected an t-BHP-induced increase in levels of oxidative stress parameters of diabetic erythrocytes

scholarly journals Serum Levels of Progranulin Are Closely Associated with Microvascular Complication in Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lin Xu ◽  
Bo Zhou ◽  
Huixia Li ◽  
Jiali Liu ◽  
Junhui Du ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Microvascular Complications ◽  
Linear Regression Analysis ◽  
Serum Levels ◽  
Diabetic Microangiopathy ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Objective. Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the correlation between PGRN and type 2 diabetics with microvascular complications.Methods. PGRN serum levels and glucose metabolism related substance were measured in 84 type 2 diabetic patients with or without microangiopathies and 12 health persons. Further analyses of serum PGRN in different stages of diabetic microangiopathies were conducted.Results. Serum levels of PGRN were markedly higher in type 2 diabetic patients with microangiopathies. PGRN serum levels increased with the progress of diabetic microangiopathies with significantly highest values detectable in clinical diabetic nephropathy (CDN) and proliferative diabetic retinopathy (PDR) groups. Serum PGRN concentrations in all individuals positively and markedly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), urinary albumin excretion rate (UAER), blood urea nitrogen (BUN), creatinine (CRE), white blood cell (WBC), disease duration, IL-6, and TNF-α, while correlating negatively and significantly with eGFR. Multiple linear regression analysis showed that only UAER and CRE were independently associated with serum PGRN.Conclusion. PGRN might be considered as a marker for diabetic microangiopathy and its severity.

Comparative metabolism of Radix scutellariae extract by intestinal bacteria from normal and type 2 diabetic mice in vitro

2014 ◽  
Vol 153 (2) ◽  
pp. 368-374 ◽  
Author(s):  
Jun Xu ◽  
Min Zhao ◽  
Dawei Qian ◽  
Er-xin Shang ◽  
Shu Jiang ◽  
...  
Keyword(s):  
Intestinal Bacteria ◽  
Diabetic Mice ◽  
Comparative Metabolism ◽  
Radix Scutellariae ◽  
Type 2 Diabetic

scholarly journals Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

2015 ◽  
Vol 308 (4) ◽  
pp. H291-H302 ◽  
Author(s):  
Niraj M. Bhatt ◽  
Miguel A. Aon ◽  
Carlo G. Tocchetti ◽  
Xiaoxu Shen ◽  
Swati Dey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Negative Impact ◽  
Antioxidant Activities ◽  
Contractile Function ◽  
Heart Function ◽  
Redox Balance ◽  
The Impact ◽  
Type 2 Diabetic

Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function.

scholarly journals Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Mei-Fang Zhong ◽  
Wei-Li Shen ◽  
Masaki Tabuchi ◽  
Kyoko Nakamura ◽  
Yi-Chen Chen ◽  
...  
Keyword(s):  
Insulin Level ◽  
Insulin Injection ◽  
Diabetic Rats ◽  
Endothelium Dysfunction ◽  
Mild Hyperglycemia ◽  
Oxide Synthase ◽  
Type 2 Diabetic ◽  
Inducible Nitric Oxide

We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarityin vitroenhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.

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