scholarly journals Potentiation of Acetylcholine-Induced Relaxation of Aorta in Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Sex-Specific Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Farjana Akther ◽  
Md Rahatullah Razan ◽  
Sonali Shaligram ◽  
James L. Graham ◽  
Kimber L. Stanhope ◽  
...  

Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. The objectives of this study were to examine whether there were (1) sex differences in aortic function and (2) alterations in the relative contribution of endothelium-derived relaxing factors in modulating aortic reactivity in UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine (ACh) was measured in aortic rings before and after exposure to pharmacological inhibitors. Relaxation responses to sodium nitroprusside were assessed in endothelium-denuded rings. Moreover, contractile responses to phenylephrine (PE) were measured before and after incubation of aortic rings with a nitric oxide synthase (NOS) inhibitor in the presence of indomethacin. Metabolic parameters and expression of molecules associated with vascular and insulin signaling as well as reactive oxygen species generation were determined. Diabetes slightly but significantly impaired EDV in response to ACh in aortas from females but potentiated the relaxation response in males. The potentiation of EDV in diabetic male aortas was accompanied by a traces of nitric oxide (NO)- and prostanoid-independent relaxation and elevated aortic expression of small- and intermediate conductance Ca2+-activated K+ channels in this group. The smooth muscle sensitivity to NO was not altered, whereas the responsiveness to PE was significantly enhanced in aortas of diabetic groups in both sexes. Endothelium-derived NO during smooth muscle contraction, as assessed by the potentiation of the response to PE after NOS inhibition, was reduced in aortas of diabetic rats regardless of sex. Accordingly, decreases in pAkt and peNOS were observed in aortas from diabetic rats in both sexes compared with controls. Our data suggest that a decrease in insulin sensitivity via pAkt-peNOS-dependent signaling and an increase in oxidative stress may contribute to the elevated contractile responses observed in diabetic aortas in both sexes. This study demonstrates that aortic function in UCD-T2DM rats is altered in both sexes. Here, we provide the first evidence of sexual dimorphism in aortic relaxation in UCD-T2DM rats.

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.


2014 ◽  
Vol 58 (4) ◽  
pp. 369-376 ◽  
Author(s):  
Joelma Ines Tagliapietra Barros ◽  
Francisco Vagnaldo Fechine ◽  
Renan Magalhães Montenegro Júnior ◽  
Otoni Cardoso do Vale ◽  
Virgínia Oliveira Fernandes ◽  
...  

Objective: To evaluate the effect of sitagliptin on somatosensory-evoked potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus without clinical diabetic neuropathy. Materials and methods: Interventional, prospective, and open study. Patients with less than six months from the diagnosis were included. Examinations of SEPs and laboratory tests at fasting and after food stimulation were performed before and after three months of treatment with sitagliptin (100 mg/day). Results: There was a reduction in the mean levels of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P = 0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of the study (P = 0.0025). Several SEPs showed statistically significant differences when analyzed before and after treatment with sitagliptin. Conclusion: The results give a glimpse of the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system, in addition to its already established role in glycemic control.


2020 ◽  
Author(s):  
Wenhao Song ◽  
Yao Gong ◽  
Pei Tu ◽  
Lin Zhang ◽  
Zhili Jin ◽  
...  

Abstract Background The aim of this study was to analyze the expressions of long noncoding RNA(lncRNA) in rat with type 2 diabetes mellitus(T2DM) complicated with acute myocardial ischemia reperfusion injury(IRI). Methods Type 2 diabetic rats were induced by high calorie diet combined with streptozotocin. IRI rats models were established by the ligation and release of left anterior descending coronary artery(LAD). The expression levels of lncRNA and mRNA in myocardial tissues of rats were detected via high-throughput sequencing technology, and Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Result Transcriptome analyses were performed to show expression profiles of mRNAs and lncRNAs in myocardial tissues of diabetic rats with IRI. A total of 2,476 lncRNAs and 710 mRNAs were differentially expressed between operation group and sham operation group. Then, an mRNA-lncRNA coexpression network was constructed. Finally, the present study verified that TCONS_00036439、TCONS_00151548、TCONS_00153276、TCONS_00344188、TCONS_00277692、TCONS_00236469、TCONS_00236468、TCONS_00153290、TCONS_00360941、TCONS_00142622 were associated with the initiation and development of ischemia reperfusion injury. Then, an lncRNA-mRNA coexpression network was constructed. Conclusion There is differential expression of lncRNAs in myocardial IRI tissues of diabetic rats. Building gene regulation networks to find the nodal gene and lncRNA is useful for understanding the pathogenesis of type 2 diabetes mellitus complicated with acute myocardial ischemia reperfusion injury and providing new therapy target.


2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 3-7 ◽  
Author(s):  
Cacio Ricardo WIETZYCOSKI ◽  
João Caetano Dallegrave MARCHESINI ◽  
Sultan AL-THEMYAT ◽  
Fabiola Shons MEYER ◽  
Manoel Roberto Maciel TRINDADE

ABSTRACT Background: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications Aim: To demonstrate alterations in oxidative stress after metabolic surgery. Methods: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats.


Nitric Oxide ◽  
2007 ◽  
Vol 16 (3) ◽  
pp. 348-355 ◽  
Author(s):  
Valeria C. Sandrim ◽  
Roger W.C. de Syllos ◽  
Hugo R.K. Lisboa ◽  
Glaucia S. Tres ◽  
Jose E. Tanus-Santos

Author(s):  
Yusi Anggriani ◽  
Agus Purwanggana ◽  
Mita Restinia

Objective: This study was carried out to analyze the impact of universal health coverage in Indonesia, known as Jaminan Kesehatan Nasional (JKN) on percentage of patients who did fasting blood glucose (FBG) tests each hospital visit and clinical outcomes (CO) in type 2 diabetes mellitus (T2DM) patients.Methods: We conducted a longitudinal retrospective study to collect the data from 6-month before JKN and 1-year after JKN at 3 hospitals in Jakarta Province. All T2DM outpatients’ services using Asuransi Kesehatan (ASKES) with at least 6 hospital visits were included. The subject with double insurances and died before implementation of JKN were excluded. The clinical outcome before and after JKN were compared with Wilcoxon test.Results: Total samples that collected were 296 patients divided to predominance female with 166(56%) and male 125(44%). From the data, it seemed that there were no all patients who did FBG test. We founded 50% of patients had FBG test before JKN.  Meanwhile, the percentage at the beginning of JKN tended to be lower about 37% than before JKN. Number of patiens decreased associate with JKN but number of hospital visit increased. Based on FBG level, 17(9.19%) patients had better CO and this number increased slightly after JKN to 22(11.89%). In contrast, patients with worse FBG level decreased about 9%. More patients had bad stable and less patients had good stable FBG level. Statistical analysis showed that CO between before and after JKN had P value 0.404 among T2DM outpatients in Type A Hospitals and P value 0.877 in Type B Hospital.Conclusion: Implementation of JKN had impact to decrease percentage of patients who did FBG tests and number of patients but raised hospital visit. CO was different significantly between before and after JKN among T2DM outpatients in Type A Hospitals but was no different in Type B Hospital.Keywords: Universal health coverage, Clinical outcome, Type 2 diabetes mellitus, Fasting blood glucose.


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