Anti-metabolic syndrome effects of adenosine ingestion in stroke-prone spontaneously hypertensive rats fed a high-fat diet

Abstract

We have demonstrated previously that both acute and chronic oral administration of adenosine have novel functions such as anti-hypertensive effects and improved hyperlipidaemia in stroke-prone spontaneously hypertensive rats (SHRSP) fed a normal diet. The purpose of the present study was to investigate the effect of adenosine administration on metabolic syndrome-related parameters in SHRSP fed a high-fat diet. Six-week-old rats were divided into three groups, and were administered either water (control) or adenosine (10 or 100 mg/l) for 8 weeks. During this period, the rats had free access to a high-fat diet based on AIN-93M. The results showed that hypertension, plasma lipid, NO, insulin, glucose and urinary 8-hydroxy-2 0 -deoxyguanosine levels improved significantly in both adenosine groups. The mRNA expression levels of genes involved in anti-oxidative activity and adenosine receptors were also altered in the adenosine groups. Administration of adenosine also increased plasma adiponectin levels, accompanied by upregulation of mRNA expression level of adiponectin and adiponectin receptor 1 in perirenal fat and adiponectin receptor 2 in the liver. In conclusion, oral administration of adenosine is effective for improving metabolic syndrome-related parameters in SHRSP, and accordingly it may prevent the progression of the metabolic syndrome. High-fat diet: Blood pressure: Glucose metabolism: Lipid profileObesity has become increasingly prevalent worldwide as a result of changes in lifestyle, especially eating habits, and it is involved in the aetiology of a number of conditions such as CVD, hypertension, stroke and diabetes (1,2) . Overconsumption of high-energy food and lower energy expenditure have resulted in an alarming increase in the incidence of obesity (3) . The fact that clinically diagnosed insulin resistance, hypertension, increased fat distribution and high plasma TAG levels have been associated with the development of diseases associated with metabolic syndrome-related parameters has attracted attention from the scientific community. Prevention and improvement of obesity and metabolic syndrome-related diseases are therefore important issues in modern society, and represent an effective strategy for the promotion of better health.Adenosine is an endogenous purine nucleoside that modulates many physiological processes, with these effects being mediated by the activation of specific subtypes of adenosine receptors, termed A 1 , A 2A , A 2B and A 3 ( 4,5) . Adenosine can be extracted from plant and mammalian tissues. Higher adenosine concentrations in the plant and mammalian tissues result from enhanced excretion of adenosine or diminished uptake of adenosine (6) . Previous studies have provided evidence to support the physiological role of adenosine in general health. For example, studies in both rats and human subjects showed that oral administration of adenosine in sucrose solutions decreased blood glucose and insulin concentrations due to its inhibitory effect on a-glucosidase (7,8) . Continuous int...

The Adenosine–Insulin Signaling Axis in the Fetoplacental Endothelial Dysfunction in Gestational Diabetes

“…Insulin sensitivity is increased in rats supplemented with adenosine in the diet (Ardiansyah et al, 2010). These data are complemented by similar observations described in diabetic rat adipocytes (Joost & Steinfelder, 1982), nondiabetic rat skeletal muscle (Vergauwen et al, 1995), and patients with TIDM who received an infusion of adenosine (Srinivasan et al, 2005) (Table 3).…”

“…Moreover, the expression and activation of adenosine receptors reduces plasma levels of D-glucose, due to increased release and the biological effect of insulin in diabetic rats (Johansson et al, 2006;Németh et al, 2007;Töpfer et al, 2008). Activation of A 1 AR (Vergauwen et al, 1994) or decreased expression A 2B AR (Ardiansyah et al, 2010;Figler et al, 2011), results in an increased sensitivity to insulin, but there is no information about the specific mechanisms explaining the biological actions of adenosine (Burnstock et al, 2006;San Martín & Sobrevia, 2006;Mundell & Kelly, 2010). The activation of the A 2B AR, but to a lesser degree than the A 1 AR, prevents the development of diabetes in mouse (Németh et al, 2007).…”

Insulin therapy and fetoplacental vascular function in gestational diabetes mellitus

“…Furthermore, it is also unknown whether the responses to insulin mediated via IR-A or IR-B in these cell types are modulated by AR-associated (potentially A 2A AR and A 1 AR) cell signalling mechanisms. Based on the fact that activation of ARs modulates the biological effects of insulin in several other cell types (Vergauwen et al 1994;Ardiansyah et al 2010;Fredholm, 2014), including other pathologies of pregnancy such as in late onset pre-eclampsia , we hypothesize that insulin offers a beneficial effect in the fetoplacental endothelium of GDM pregnancies based on a differential expression of ARs and IRs via a specific functional relationship between these receptors and their associated cell signalling mechanisms in the human placental endothelium.…”

“…; Ardiansyah et al . ; Fredholm, ), including other pathologies of pregnancy such as in late onset pre‐eclampsia (Salsoso et al . ), we hypothesize that insulin offers a beneficial effect in the fetoplacental endothelium of GDM pregnancies based on a differential expression of ARs and IRs via a specific functional relationship between these receptors and their associated cell signalling mechanisms in the human placental endothelium.…”

Gestational Diabetes - Causes, Diagnosis and Treatment

“…or decreased expression A 2B AR(Ardiansyah et al, 2010;Figler et al, 2011), results in an increased sensitivity to insulin, but there is no information about the specific mechanisms explaining the biological actions of adenosine(Burnstock et al, 2006; San Martín & Sobrevia, 2006;Mundell & Kelly, 2010…”