Beneficial effects of pyridoxamine in endothelial dysfunction of type 2 diabetic animal models

2021 ◽  
Vol 331 ◽  
pp. e100
Author(s):  
C. Sena ◽  
D. Carvalho ◽  
A. Pereira ◽  
M. Queiroz ◽  
R. Seiça
Keyword(s):  
Endothelial Dysfunction ◽  
Animal Models ◽  
Diabetic Animal ◽  
Beneficial Effects ◽  
Type 2 Diabetic

scholarly journals Spontaneous Type 2 Diabetic Rodent Models

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Health Care ◽  
Animal Models ◽  
Rodent Models ◽  
Advantages And Disadvantages ◽  
Characteristic Features ◽  
Type 2 Diabetic

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.

scholarly journals An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Levels ◽  
Type 2 Diabetic

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

Angiotensin II causes endothelial dysfunction via the GRK2/Akt/eNOS pathway in aortas from a murine type 2 diabetic model

2011 ◽  
Vol 64 (5) ◽  
pp. 535-546 ◽  
Author(s):  
Kumiko Taguchi ◽  
Tsuneo Kobayashi ◽  
Yasuhiro Takenouchi ◽  
Takayuki Matsumoto ◽  
Katsuo Kamata
Keyword(s):  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Diabetic Model ◽  
Type 2 Diabetic

Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated Type 2 diabetic patients

2010 ◽  
Vol 118 (10) ◽  
pp. 607-615 ◽  
Author(s):  
Sandra J. Hamilton ◽  
Gerard T. Chew ◽  
Timothy M.E. Davis ◽  
Gerald F. Watts
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Statin Therapy ◽  
Brachial Artery ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15 statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)-cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow-mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145 mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated dilatation) were measured by ultrasonography at the start and end of each treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apo (apolipoprotein) concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1±0.6 compared with −0.3±0.6%, P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100 ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with −1.5 (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P≤0.03), but did not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=−0.61, P=0.02) and apoB-100 (r=−0.54, P=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.

scholarly journals Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the KATP/MAPK pathway

2019 ◽  
Vol 317 (1) ◽  
pp. C68-C81 ◽  
Author(s):  
Yihan Wang ◽  
Leo M. Hall ◽  
Marisa Kujawa ◽  
Hainan Li ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Network Formation ◽  
Cell Function ◽  
Mapk Pathway ◽  
Endothelial Cell Dysfunction ◽  
Endothelial Cell Function ◽  
Cell Dysfunction ◽  
Type 2 Diabetic

Endothelial dysfunction is a key risk factor in diabetes-related multiorgan damage. Methylglyoxal (MGO), a highly reactive dicarbonyl generated primarily as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids, and lipids, resulting in structural and functional changes. MGO can also form advanced glycation end products (AGEs). How MGO causes endothelial cell dysfunction, however, is not clear. Human aortic endothelial cells (HAECs) from healthy (H-HAECs) and type 2 diabetic (D-HAECs) donors were cultured in endothelial growth medium (EGM-2). D-HAECs demonstrated impaired network formation (on Matrigel) and proliferation (MTT assay), as well as increased apoptosis (caspase-3/7 activity and TUNEL staining), compared with H-HAECs. High glucose (25 mM) or AGEs (200 ng/ml) did not induce such immediate, detrimental effects as MGO (10 µM). H-HAECs were treated with MGO (10 µM) for 24 h with or without the ATP-sensitive potassium (KATP) channel antagonist glibenclamide (1 µM). MGO significantly impaired H-HAEC network formation and proliferation and induced cell apoptosis, which was reversed by glibenclamide. Furthermore, siRNA against the KATP channel protein Kir6.1 significantly inhibited endothelial cell function at basal status but rescued impaired endothelial cell function upon MGO exposure. Meanwhile, activation of MAPK pathways p38 kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) (determined by Western blot analyses of their phosphorylated forms, p-JNK, p-p38, and p-ERK) in D-HAECs were significantly enhanced compared with those in H-HAECs. MGO exposure enhanced the activation of all three MAPK pathways in H-HAECs, whereas glibenclamide reversed the activation of p-stress-activated protein kinase/JNK induced by MGO. Glyoxalase-1 (GLO1) is the endogenous MGO-detoxifying enzyme. In healthy mice that received an inhibitor of GLO1, MGO deposition in aortic wall was enhanced and endothelial cell sprouting from isolated aortic segment was significantly inhibited. Our data suggest that MGO triggers endothelial cell dysfunction by activating the JNK/p38 MAPK pathway. This effect arises partly through activation of KATP channels. By understanding how MGO induces endothelial dysfunction, our study may provide useful information for developing MGO-targeted interventions to treat vascular disorders in diabetes.

Sign in / Sign up

Export Citation Format

Share Document