scholarly journals Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaozhen Wang ◽  
Wenwen Fu ◽  
Yan Xue ◽  
Zeyuan Lu ◽  
Yuangeng Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Vascular Complications ◽  
Health Concern ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Anti Inflammatory ◽  
Ginsenoside Rc

Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.

scholarly journals METFORMIN USE IN DIABETES PRIOR TO HOSPITALIZATION: EFFECTS ON MORTALITY IN COVID-19

2020 ◽  
Vol 26 (10) ◽  
pp. 1166-1172
Author(s):  
Jinghong Li ◽  
Qi Wei ◽  
Willis X. Li ◽  
Karen C. McCowen ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Data ◽  
Laboratory Data ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort ( P = .02). Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM. Abbreviations: ACE2 = angiotensin-converting enzyme 2; AMPK = AMP-activated protein kinase; BMI = body mass index; COVID-19 = coronavirus disease 2019; SARSCoV-2 = severe acute respiratory syndrome coronavirus 2; T2DM = type 2 diabetes mellitus

P0527HYPERGLYCEMIA-ASSOCIATED ACUTE KIDNEY INJURY INCREASES THE SUSCEPTIBILITY TOWARDS NEUROLOGICAL DYSFUNCTION: ROLE OF ANGIOTENSIN II TYPE 2 RECEPTOR AND ANGIOTENSIN-CONVERTING ENZYME 2

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nisha Sharma ◽  
Anil Bhanudas Gaikwad
Keyword(s):  
Angiotensin Ii ◽  
Combination Therapy ◽  
Angiotensin Converting Enzyme ◽  
Neurological Dysfunction ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Abstract Background and Aims In clinical settings, diabetics remain on higher risk of ischemic renal injury (IRI) than nondiabetic patients. In addition, IRI predisposes distant organs to dysfunction such as neurological impairments via activation of the pressor arm of renin-angiotensin system (RAS). In contrast, the role of depressor arm of RAS on IRI-associated neurological sequalae remains elusive. Hence, this study explored the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) in IRI-associated neurological dysfunctions under nondiabetic (ND) and diabetes mellitus (DM) condition. Method Type 1 diabetes was induced by injecting streptozotocin (55 mg/kg i.p.). ND and DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or in combination therapy. Behavioural, biochemical, and histopathological analysis were done to assess IRI-induced neurological impairment. Moreover, immunohistochemistry, ELISA and qRT-PCR experiments were conducted for molecular mechanism analysis. Result In ND and DM rats, IRI caused hippocampal complications as evidenced by increased MDA and nitrite levels, augmented inflammatory cytokines (granulocyte colony stimulating factor, glial fibrillary acidic protein), altered protein and mRNA expressions of Ang II, Ang-(1-7), AT1R, AT2R and MasR. In contrast, concomitant therapy of C21 and Dize effectively normalised aforementioned hippocampal alterations. The protective effect of combination therapy was exerted due to augmented protein and mRNA levels of depressor arm components. Conclusion The current study demonstrated the protective role of AT2R agonist and ACE2 activator in IRI-associated neurological dysfunction through preventing oxidative stress, inflammation and upregulating brain depressor arm of RAS under ND and DM conditions.

scholarly journals Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

2021 ◽  
Vol 7 ◽  
Author(s):  
Jacob Roberts ◽  
Antonia L. Pritchard ◽  
Andrew T. Treweeke ◽  
Adriano G. Rossi ◽  
Nicole Brace ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Inflammatory Responses ◽  
Severe Form ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Inflammatory Processes ◽  
Meta Analyses

Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.

scholarly journals MO626EFFECTS OF RAMIPRIL IN LUNG AND KIDNEY ANGIOTENSIN CONVERTING ENZYME 2 (ACE2) EXPRESSION IN A TYPE 2 DIABETIC MURINE MODEL: LESSONS FOR COVID-19 INFECTION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ander Vergara Arana ◽  
Conxita Jacobs Cachá ◽  
Mireia Molina ◽  
Pamela Dominguez ◽  
Begoña Benito ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzymatic Activity ◽  
Mrna Expression ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Diabetic Mice ◽  
Angiotensin Converting Enzyme 2 ◽  
Ras Blockers ◽  
Activity Decrease

Abstract Background and Aims Angiotensin converting enzyme 2 (ACE2) is one of the components of the renin-angiotensin system (RAS) that mainly degrades angiotensin II to angiotensin-(1-7). ACE2 is predominantly expressed in the kidney and the heart, but it has been evidenced in type 2 alveolar lung cells, where it acts as a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, a controversy arose as to whether the use of RAS blockers could increase ACE2 lung expression and the risk infection by COVID-19. This study aimed to investigate the effect of an ACE inhibitor (Ramipril) on ACE2 expression in experimental diabetes. Method 12 weeks old diabetic db/db mice (n=7) were given ramipril (8 mg/Kg/day) during 8 weeks or the respective vehicle. db/m (n=7) vehicle-treated non-diabetic mice were included as controls. ACE2 mRNA expression and enzymatic activity were studied in kidney, heart and lung samples of these animals to identify if the diabetic condition or treatment with ramipril modulated ACE2 expression. Results In vehicle-treated diabetic db/db animals, ACE2 mRNA expression was significantly increased in the kidney (p<0.001) and ramipril treatment reversed this effect (p=0.026). In the heart, ACE2 expression decreased in db/db when compared to db/m littermates (p=0.035) and ramipril had no effect. We found no differences in ACE2 gene expression in the lung. Besides, ACE2 enzymatic activity was increased in the kidney (29%) and also in the lung (16%) of db/db mice when compared to controls. Ramipril treatment decreased ACE2 activity a 19% in the lung and had no effect in the kidney when compared to untreated db/db (see figure). In the heart, ACE2 activity tended to decrease in db/db mice (29%) when compared to db/m and ramipril increased ACE2 activity (18%) but did not exceed the cardiac ACE2 activity of the db/m. Conclusion ACE2 is increased in the kidney and the lung, and decreased in the heart of diabetic mice. Ramipril treatment restores ACE2 levels. The results suggest that ACE inhibitors do not increase ACE2 expression and the activity decrease exerted in the lung may be protective against COVID-19 infection.

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