The Renin-Angiotensin System in the Pathophysiology of Type 2 Diabetes

Goossens, Gijs H.

doi:10.1159/000342776

Cited by 76 publications

(50 citation statements)

References 253 publications

(172 reference statements)

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“…On a different matter, an up regulation of RAAS in their cardiovascular system has been found in individuals with type 2 diabetes. An up regulated RAAS may contribute to the development of many diabetic complications, including microvascular and macrovascular diseases [110, 111], in addition, it has been shown that the up regulation of Ang II and the activation of mineralocorticoid receptor by aldosterone might promote insulin resistance through activation of the mTOR–S6K1 signal transduction pathway by inducing phosphorylation in serine residues of IRS [112] (Fig. 2).…”

Section: Insulin Resistance Hypertension and Endothelial Dysfunctionmentioning

confidence: 99%

Association between insulin resistance and the development of cardiovascular disease

Ormazábal

Nair

Elfeky

et al. 2018

Cardiovasc Diabetol

1,434

950

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For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

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Section: Insulin Resistance Hypertension and Endothelial Dysfunctionmentioning

confidence: 99%

Association between insulin resistance and the development of cardiovascular disease

Ormazábal

Nair

Elfeky

et al. 2018

Cardiovasc Diabetol

1,434

950

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“…rowing evidence suggests that increased activation of the renin-angiotensin system (RAS) is related to insulin resistance and ␤-cell dysfunction (1)(2)(3). Recently, the NAVIGATOR trial demonstrated that treatment with the angiotensin II type 1 receptor blocker valsartan (VAL) for 5 years, in addition to lifestyle modification, reduced the incidence of type 2 diabetes mellitus (T2DM) by 14% (4).…”

mentioning

confidence: 99%

“…In addition, intrinsic disturbances in skeletal muscle fatty acid (FA) handling may contribute to lipid accumulation (7)(8)(9). Studies in rodents and humans have shown that RAS blockade decreased adipocyte size and increased mitochondrial function and insulin signaling in skeletal muscle (1). Therefore, it is tempting to postulate that reduced lipid overflow and/or altered skeletal muscle FA handling may underlie the beneficial effects of RAS blockade on insulin sensitivity.…”

mentioning

confidence: 99%

The Effects of Long-Term Valsartan Treatment on Skeletal Muscle Fatty Acid Handling in Humans With Impaired Glucose Metabolism

Moors

Blaak

Zijl

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:Blocking the renin-angiotensin system reduces the incidence of type 2 diabetes mellitus in humans with impaired glucose metabolism (IGM). Nevertheless, underlying mechanisms remain to be established. Objective:The purpose of this study was to investigate the effects of the angiotensin II type 1 receptor blocker valsartan (VAL) on skeletal muscle fatty acid (FA) handling in subjects with IGM. G rowing evidence suggests that increased activation of the renin-angiotensin system (RAS) is related to insulin resistance and ␤-cell dysfunction (1-3). Recently, the NAVIGATOR trial demonstrated that treatment with the angiotensin II type 1 receptor blocker valsartan (VAL) for 5 years, in addition to lifestyle modification, reduced the incidence of type 2 diabetes mellitus (T2DM) by 14% (4). We have recently demonstrated that 26 weeks of VAL Design

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“…Thus, suppressing RAAS activity can contribute to the prevention of diseases such as DM-2 through enhanced insulin release and sensitivity. 11 The effects of insulin can be downregulated by angiotensin II, since this hormone is able to stimulate phosphorylation of tyrosine in the insulin receptors (IRS-1 and IRS-2), as well as their associations with PI-3 kinase, inhibiting this enzyme. 12 This phenomenon can be prevented by the use of angiotensin II receptor (AT1) blockers.…”

Section: Introductionmentioning

confidence: 99%

Effect of aquatic exercise training on lipids profile and glycaemia: A systematic review

Delevatti

Marson

Kruel

2015

Revista Andaluza de Medicina del Deporte

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a b s t r a c tThe objective of this study was to investigate the acute and chronic effects of aquatic exercise training on glycaemia and lipids profile. A systematic review of clinical trials was performed assessing the effects of aquatic exercise and/or training in upright position on lipids profile and glycaemic index. Two raters independently assessed the eligibility criteria and the methodological quality of the studies using the PEDro scale. Average and standard deviation of all variables significantly altered by the interventions were extracted for calculating percentage alterations. Three studies involving the acute effect of aquatic aerobic exercise on the variables of interest were analysed, with two of them demonstrating the efficacy of this type of training in improving lipids profile. Nine studies involving the chronic effects of aquatic training on the same variables were also analysed; eight of them, which assessed different training interventions for different populations, reported benefits of exercise regarding these variables. In conclusion, the improvements found in response to aquatic exercise training in upright position in glycaemia and lipids profile indicate the aquatic environment as a favourable environment for conducting exercise programmes. Efecto del entrenamiento acuático en el perfil lipídico y la glicemia: una revisión sistemáticaPalabras clave: Ejercicio acuático Metabolismo de glucosa Metabolismo de lípidos r e s u m e n El objetivo de este estudio fue investigar los efectos agudos y crónicos del entrenamiento acuático en el perfil lipídico y la glucemia. Se llevó a cabo una revisión sistemática valorando los efectos del ejercicio acuático y/o el entrenamiento en posición erecta sobre índices lipídicos y glucémicos. Dos investigadores valoraron independientemente los criterios de selección y la calidad metodológica de los estudios mediante la escala PEDro. La media y la desviación estándar de todas las variables que se alteraron significativamente por las intervenciones fueron extraídas para calcular el porcentaje de alteración. Se analizaron tres estudios relativos al efecto agudo del ejercicio aeróbico acuático en las variables de interés, dos de ellos demostraron la eficacia de este tipo de entrenamiento sobre el perfil lipídico. Se analizaron también nueve estudios relativos al efecto crónico del entrenamiento acuático sobre las mismas variables, ocho de ellos que valoraron diferentes intervenciones en el entrenamiento con distintas poblaciones, encontraron beneficios del ejercicio en relación a estas variables. En conclusión, las mejoras

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The Renin-Angiotensin System in the Pathophysiology of Type 2 Diabetes

Cited by 76 publications

References 253 publications

Association between insulin resistance and the development of cardiovascular disease

Association between insulin resistance and the development of cardiovascular disease

The Effects of Long-Term Valsartan Treatment on Skeletal Muscle Fatty Acid Handling in Humans With Impaired Glucose Metabolism

Effect of aquatic exercise training on lipids profile and glycaemia: A systematic review

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