Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes.

Aim: The effects of exercise intervention and to assess its long-term efficacy in preventing subsequent cardiovascular events in patients with type 2 diabetes were little known on randomized controlled trial.

Methods: Thirty-eight type 2 diabetic patients (21 men and 17 women) were assigned to either the exercise group (n=21) or the control group without exercise training (n=17) by simple randomization. The exercise training group was scheduled for aerobic and resistance exercise programs for 3 months.

Reciprocal regulation of natriuretic peptide receptors by insulin in adipose cells.

Atrial- and brain-type natriuretic peptides (ANP and BNP, respectively) have been shown to exert potent lipolytic action in adipocytes. A family of natriuretic peptide receptors (NPRs), NPR-1, NPR-2, and NPR-3, mediates their physiologic effects. NPR-1 and NPR-2 are receptor guanylyl cyclases, while NPR-3 lacks enzymatic activity and functions primarily as a clearance receptor for natriuretic peptides.

Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice.

Aims: In obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation in heart, kidney, and vasculature via ROS generation.

[Human genetic mutations and polymorphisms of adipocytokines relating to obesity].

Human gene mutations and polymorphisms of adipocytokines, adipocyte-derived bioactive molecules, have been reported to be implicated in the pathogenesis of obesity. Leptin and its receptor gene mutations are well-established in the development of severe obesity. Among early onset severe obese patients, the prevalence of various leptin-receptor gene mutations was about 3%.

Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha.

Objective: Adiponectin is recognized as an antidiabetic, antiatherosclerotic, and anti-inflammatory protein derived from adipocytes. However, the role of adiponectin in cardiac fibrosis remains uncertain. We herein explore the effects of adiponectin on cardiac fibrosis induced by angiotensin II (Ang II).

Clinical significance of high-molecular weight form of adiponectin in male patients with coronary artery disease.

Background: It has been reported previously that the measurement of plasma total adiponectin level is clinically useful to estimate the risk of coronary artery disease (CAD). Here, the relevance of high molecular weight (HMW) adiponectin with risk factors for atherosclerosis is investigated

Methods And Results: A total of 186 consecutive male CAD patients participated in the study and were categorized into quartiles based on their total adiponectin level. The interquartile cut-off points were 4.

Impaired flow-mediated vasodilatation and insulin resistance in type 2 diabetic patients with albuminuria.

An elevated urinary albumin excretion is associated with an increased risk of cardiovascular disease due to atherosclerosis, but the pathophysiological mechanism underlying this association is poorly understood. We studied 217 diabetic patients, that is, 121 normoalbuminuric patients, 71 microalbuminuric patients, and 25 macroalbuminuric patients. We evaluated flow-mediated dilatation of brachial artery (%FMD, one endothelial function marker associated with endogenous NO production), von Willebrand factor (vWF, endothelial activation marker), high-sensitive CRP (hsCRP, a low-grade inflammation marker), asymmetric dimethyl arginine (ADMA, an endogenous inhibitor of NO synthesis), and insulin sensitivity by steady-state plasma glucose method.

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

Objective: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease.

Adiponectin replenishment ameliorates obesity-related hypertension.

Patients with obesity are susceptible to hypertension. We have reported that the plasma adiponectin levels are decreased in obesity and that adiponectin has many defensive properties against obesity-related diseases, such as type 2 diabetes and coronary artery disease. The aim of this study was to determine the relationship between adiponectin and hypertension in mice.

Pioglitazone-induced insulin sensitization improves vascular endothelial function in nondiabetic patients with essential hypertension.

Background: It has been suggested that insulin resistance is involved in the impaired vascular endothelial function not only in diabetic patients but also in hypertensive patients. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse endothelial dysfunction in hypertensive subjects.

Methods: Fifteen nondiabetic patients with essential hypertension were enrolled in this study.

Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.

Background: Left ventricular (LV) hypertrophy and diastolic dysfunction, which are common cardiac consequences of hypertension, are modified by insulin resistance. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse such cardiac changes in hypertensive patients.

Methods: A total of 30 patients with essential hypertension were enrolled in this study.

Plasma asymmetric dimethylarginine and coronary and peripheral endothelial dysfunction in hypertensive patients.

Background: The attenuation of coronary flow reserve (CFR) and endothelium-mediated vasodilation of the brachial artery (EMV-BA) have been frequently reported in hypertensive patients. The present study investigated the link between CFR and EMV-BA in hypertensive patients. We hypothesized that changes in serum asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and concomitant insulin resistance may be underlying factors connecting the two pathologic alterations.

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension.

Background: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening.

Methods: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening.