scholarly journals Altered Jagged1-Notch1 Signaling in Enhanced Dysfunctional Neovascularization and Delayed Angiogenesis After Ischemic Stroke in HFD/STZ Induced Type 2 Diabetes Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Guo ◽  
Jia Jia ◽  
Yanling Tu ◽  
Chang Jin ◽  
Cen Guo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Repair Process ◽  
Diabetic Rats ◽  
Notch1 Signaling ◽  
Blood Brain Barrier Disruption ◽  
Before And After ◽  
Brain Barrier Disruption

Diabetes exacerbates brain damage in cerebral ischemic stroke. Our previous study has demonstrated that after cerebral ischemia, type 2 diabetes rats displayed worse neurological outcomes, larger cerebral infarction and severer blood-brain barrier disruption. However, our knowledge of the mechanisms of how diabetes impacts the cerebrovascular repair process is limited. This study was aimed to characterize structural alterations and potential mechanisms in brain microvessels before and after ischemic stroke in type 2 diabetic rats treated with high-fat diet and streptozotocin (HFD/STZ). Furtherly, we tested our hypothesis that dysregulated intercellular Jagged1-Notch1 signaling was involved in the dysfunctional cerebral neovascularization both before and after ischemic stroke in HFD/STZ rats. In our study, we found increased yet dysfunctional neovascularization with activated Jagged1-Notch1 signaling in the cerebrovasculature before cerebral ischemia in HFD/STZ rats compared with non-diabetic rats. Furthermore, we observed delayed angiogenesis as well as suppressed Jagged1-Notch1 signaling after ischemic stroke. Our results elucidate the potential mechanisms underlying diabetes-related cerebral microvasculature dysfunction after ischemic stroke.

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 ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Smooth Muscle ◽  
Reactive Oxygen Species Generation ◽  
Diabetic Rats ◽  
Contractile Responses ◽  
Before And After

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.

scholarly journals Different Stages of Alveolar Bone Repair Process Are Compromised in the Type 2 Diabetes Condition: An Experimental Study in Rats

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 471
Author(s):  
Letícia Pitol-Palin ◽  
Fábio Roberto de Souza Batista ◽  
Pedro Henrique Silva Gomes-Ferreira ◽  
Gabriel Mulinari-Santos ◽  
Edilson Ervolino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Bone Repair ◽  
Alveolar Bone ◽  
Repair Process ◽  
Diabetic Rats ◽  
Collagen Fibers ◽  
Volume Percentage

The aim of this study was to analyze the stages of the alveolar bone repair in type 2 diabetic rats evaluating the mechanism of mineralization and bone remodeling processes after dental extraction. Forty-eight rats were divided into normoglycemic (NG) and type 2 diabetes (T2D) groups. The upper right incisor was extracted and after 3, 7, 14 and 42 days the animals were euthanized. The following analyses were performed: immunolabeling against antibodies TNFα, TGFβ, IL6, WNT, OCN and TRAP, collagen fibers maturation, microtomography and confocal microscopy. Data were submitted to statistical analysis. The immunolabeling analysis showed that the T2D presented a more pronounced alveolar inflammation than NG. Labeling of proteins responsible for bone formation and mineralization was higher in NG than T2D, which presented greater resorptive activity characterized by TRAP labeling. Also, T2D group showed a decrease in the amount of collagen fibers. Micro-CT analysis showed that T2D causes a decrease in bone volume percentage due to deficient trabecular parameters and higher porosity. The T2D bone dynamics show a loss in bone remodeling process. T2D prolongs the local inflammatory process, which impairs the organization and maturation of collagen fibers, delaying bone formation that generates impact on mineralization and bone turnover.

312-OR: Gender-Specific Effects on Hepatic Fat Metabolism in Type 2 Diabetes before and after Remission

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 312-OR
Author(s):  
AHMAD AL-MRABEH ◽  
SHADEN MELHEM ◽  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fat Metabolism ◽  
Specific Effects ◽  
Before And After ◽  
Hepatic Fat ◽  
Gender Specific

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.

scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

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.

Functional status before and after diagnosis of Type 2 diabetes

2004 ◽  
Vol 21 (7) ◽  
pp. 793-797 ◽  
Author(s):  
G. A. Nichols ◽  
J. B. Brown
Keyword(s):  
Type 2 Diabetes ◽  
Functional Status ◽  
Before And After
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