Angiotensin-(1–7) contributes to insulin-sensitizing effects of angiotensin-converting enzyme inhibition in obese mice

Loloi, Justin; Miller, Amanda J.; Bingaman, Sarah S.; Silberman, Yuval; Arnold, Amy C.

doi:10.1152/ajpendo.00281.2018

Cited by 27 publications

(30 citation statements)

References 50 publications

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“…Regarding the circulating RAS, both ACE and ACE2 activities did not change and the Ang 1–7 concentration increased ( Américo et al, 2019 ). The improvement of circulating Ang 1–7 is related to better metabolic response since the chronic systemic Ang 1–7 administration tested by other authors provided significant reduction in body weight and adipose tissue mass, decreased total cholesterol and triglycerides, increased insulin sensitivity, glucose tolerance, and decreased the expression of proinflammatory cytokines mRNA ( Bilman et al, 2012 ; Santos et al, 2012 ; Loloi et al, 2018 ). In the subcutaneous white adipose tissue, no differences were found in ACE activity and Ang II content, however, both AT1R and AT2R expression were increased.…”

Section: Physical Exercise and The Rasmentioning

confidence: 95%

Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19

Evangelista

2020

Front. Physiol.

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Recent reports have shown that the renin angiotensin system (RAS) plays an important role in the Coronavirus disease 2019 (COVID-19) because the angiotensin converting enzyme 2 is the receptor for the severe acute respiratory syndrome coronavirus 2. In addition, the balance of RAS components can be involved in the pathogenesis and progression of COVID-19, especially in patients with metabolic and cardiovascular diseases. On the other hand, physical exercise is effective to prevent and to counteract the consequences of such diseases and one of the biological mediators of the exercise adaptation is the RAS. This review was designed to highlight the connection between COVID-19 and RAS, and to discuss the role of the RAS as a mediator of the benefits of physical exercise in COVID-19 pandemic.

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Section: Physical Exercise and The Rasmentioning

confidence: 95%

Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19

Evangelista

2020

Front. Physiol.

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“…Plasma insulin levels were determined from blood samples obtained from the carotid artery at t=-5 min prior to the insulin infusion and t=120 min. Insulin sensitivity index (ISI) is defined as ISI Clamp =GIR/(GxΔI) where GIR is normalized for G (steady-state blood glucose concentration) and Δ I (difference between fasting and steady-state plasma insulin concentrations) [20].…”

Section: Hyperinsulinemic-euglycemic Clampsmentioning

confidence: 99%

Temporal Metabolic Characteristics and Transcriptomic Landscape of Islets and Liver Reveal Dynamic Pathophysiology and Interorgan Crosstalk in High-fat Diet-induced Diabetes

Gao

Jiang

et al. 2020

Preprint

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ObjectiveHyperinsulinemia and insulin resistance are co-existing characteristics of type 2 diabetes, whereas the molecular mechanism underlying this deleterious cycle remains elusive. The temporal transcriptomic landscape of core organs responsible for insulin secretion (islets) and insulin action (liver) could provide new insights.MethodsThe longitudinal profiling of glucose metabolism, insulin sensitivity, islet architecture and secretion were conducted in C57BL/6N mice fed a high-fat diet (HFD) or chow diet for 24 weeks. RNA-sequencing of islets and liver were performed once every 4 weeks. Weighted gene co-expression network analysis and Ingenuity Pathway Analysis were applied to construct networks and evaluate co-ordinated molecular interactions between islets and liver.ResultsMice exhibited progressively deteriorated glucose homeostasis with hyperinsulinemia but impaired first-phase insulin secretion after 4 weeks on HFD. Insulin, glucagon and somatostatin secretion in response to glucose with or without palmitate gradually deteriorated from dysregulation to failure. Systemic insulin resistance developed over 24 weeks with variable time course in tissue-specific insulin action. Our transcriptomic datasets outlined the impact of HFD on dynamics of islet and liver molecular network at different stages. Correlation analyses revealed that both organs jointly programmed β-cell compensatory adaption via cell proliferation at early phase and irreversible islet dysfunction by inappropriate immune response at later stage. Alternations of T cell subpopulations validated the participation of adaptive immune response through priming and amplification phases in diabetic progression.ConclusionOur data provide a comprehensive landscape of crosstalk between islets and liver in diet-induced diabetes, elucidating the development of islet dysfunction and insulin resistance.HighlightsDiet-induced diabetes is featured by transition from islet dysfunction to failureInsulin resistance develops with variable time course in different tissuesDynamics of islet and liver molecular network interplay at different stagesCell proliferation and improper immune reaction mediated interorgan crosstalkAdaptive immune response participated via priming and amplification phases

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“…Consistent with this, therapies blocking Ang II activity such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively lower blood pressure, reduce risk for diabetes, prevent deficits in cardiovascular and metabolic functions and increase lifespan in aged animals and clinical populations [ 7 , 9 , 10 , 11 ]. Of interest, ACE inhibitors and ARBs increase levels of the protective hormone Ang-(1-7), which our group and others have shown contributes to the beneficial cardiometabolic effects of these therapies in animal models of cardiovascular diseases, obesity, and diabetes [ 12 , 13 , 14 , 15 ]. Importantly, ACE inhibitors are limited in up to 11% of patients by cough due to production of kinins, and many patients are unresponsive to these therapies in terms of blood pressure control [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice

Miller

Bingaman

Mehay

et al. 2020

IJMS

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Angiotensin (Ang)-(1-7) is a beneficial renin–angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure–lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.

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Angiotensin-(1–7) contributes to insulin-sensitizing effects of angiotensin-converting enzyme inhibition in obese mice

Cited by 27 publications

References 50 publications

Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19

Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19

Temporal Metabolic Characteristics and Transcriptomic Landscape of Islets and Liver Reveal Dynamic Pathophysiology and Interorgan Crosstalk in High-fat Diet-induced Diabetes

Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice

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