Activation of ACE2/angiotensin (1–7) attenuates pancreatic β cell dedifferentiation in a high-fat-diet mouse model

Xuan, Xiuping; Gao, Fei; Ma, Xiaoyi; Huang, Chenghu; Wang, Ying; Deng, Hongjun; Wang, Shiqi; Li, Wencun; Li, Yuan

doi:10.1016/j.metabol.2017.12.003

Cited by 56 publications

(75 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mice fed a HFD showed a significant increase in body weight and liver weight compared to the control mice fed a SD, and this effect was further promoted by the ACE2 deficiency (Figures 2A, B). Consistent with our previous findings using GTT and ITT, the HFD mice exhibited impaired glucose tolerance and insulin resistance, the effect of which was more pronounced in ACE2KO mice ( Figures 2C-F) (Xuan et al, 2018). Using 18 FDG-PET/CT, we observed that the ACE2 depletion was associated with an increase in glucose uptake and metabolic activity in the liver, with a significant delay in hepatic glucose metabolism ( Figure 2G).…”

Section: Ace2 Deficiency Aggravates Glucose Intolerance and Hepatic Ssupporting

confidence: 90%

See 1 more Smart Citation

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Yang

Xuan

et al. 2020

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and represents a potential therapeutic target for NAFLD. Glucagonlike peptide-1 (GLP-1) signaling has been shown to regulate the RAS within various local tissues. In this study, we aimed to investigate the functional relationship between GLP-1 and the local RAS in the liver during NAFLD. Wild-type and ACE2 knockout mice were used to establish a high-fat-induced NAFLD model. After the mice were treated with liraglutide (a GLP-1 analogue) for 4 weeks, the key RAS component genes were upregulated in the liver of NAFLD mice. Liraglutide treatment regulated the RAS balance, preventing a reduction in fatty acid oxidation gene expression and increasing gluconeogenesis and the expression of inflammation-related genes caused by NAFLD, which were impaired in ACE2 knockout mice. Liraglutide-treated HepG2 cells exhibited activation of the ACE2/Ang1-7/Mas axis, increased fatty acid oxidation gene expression, and decreased inflammation, which could be reversed by A779 and AngII. These results indicate that the local RAS in the liver becomes overactivated in response to NAFLD. Moreover, ACE2 knockout increases the severity of liver steatosis. Liraglutide has a negative and antagonistic effect on the ACE/AngII/AT1R axis, a positive impact on the ACE2/Ang1-7/Mas axis, and is mediated through the PI3K/AKT pathway. This may represent a potential new mechanism by which liraglutide improves NAFLD.

show abstract

Section: Ace2 Deficiency Aggravates Glucose Intolerance and Hepatic Ssupporting

confidence: 90%

“…Glucose levels were measured both before (0 min) and after (15,30,60, and 90 min) the insulin injections. The area under the curve (AUC) was calculated by applying the trapezoidal rule (Xuan et al, 2018).…”

Section: Glucose and Insulin Tolerance Testsmentioning

confidence: 99%

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Yang

Xuan

et al. 2020

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This aspect is really limiting, because diabetes and altered glucose homeostasis during a condition of severe pneumonia with SARS are reported as main factors of worse prognosis and death [152]. COVID-19 could also induce new onset diabetes, by augmenting insulin resistance and/or by a direct action [155] on the islets of Langerhans; supporting this view, previous studies have shown that ACE2 can be a therapeutic target to ameliorate microcirculation in the islets [156], and ACE2 is known to be expressed by pancreatic beta cells [157][158][159][160][161][162].…”

Section: Diabetes and Covid-19mentioning

confidence: 88%

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Sardu

Gambardella

Morelli

et al. 2020

JCM

443

412

View full text Add to dashboard Cite

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

show abstract

“…We suspect that there are higher densities of ACE2 in lung alveolar epithelial cells in male patients than in female patients, which may be the underlying reason for higher morbidity in males. In addition, elevated fasting blood glucose, GGT, and LDH can be closely related to impairment of the microenvironment of the infected tissue and the damage to target cells such as beta cells in the islets, biliary epithelial cells in the liver, and myocardium cells in the heart through ACE2 and the subsequent disruption of different feedback loops [17,18]. The presence of ACE2 in bone morrow tissue can be one of the causes of the hematological changes described above.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Mortality in Patients With COVID-19: Clinical and Laboratory Parameters

Tian

Liu

Liao

et al. 2020

Open Forum Infectious Diseases

View full text Add to dashboard Cite

Background Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) have been published. However, mortality and morbidity analyses, important for better understanding the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. Methods The cohort consisted of 11 male and 3 female patients, with 9 patients aged 70 years or above, and nearly all had underlying diseases. Results Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest computed tomography scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, this cohort had high level of cytokines such as interleukin-6 in all 8 patients tested. Conclusions The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models and will be of help in understanding the pathogenesis of this disease.

show abstract

Activation of ACE2/angiotensin (1–7) attenuates pancreatic β cell dedifferentiation in a high-fat-diet mouse model

Cited by 56 publications

References 36 publications

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Analysis of Mortality in Patients With COVID-19: Clinical and Laboratory Parameters

Contact Info

Product

Resources

About