Abstract
A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1), tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results indicate that irbesartan improves stress-induced adipose tissue inflammation and insulin resistance. Our results suggests that irbesartan treatment exerts additive benefits for glucose metabolism in hypertensive patients with mental stress.
Highlights
Modern stressors are closely related to psychological threat in daily life and often sustained
Our results suggests that irbesartan treatment exerts additive benefits for glucose metabolism in hypertensive patients with mental stress
We demonstrated that two-week intermittent restraint stress enhanced chronic inflammation of the adipose tissue and resulted in impairment of insulin sensitivity [5]
Summary
Modern stressors are closely related to psychological threat (e.g., work stress, social anxiety, and natural disasters) in daily life and often sustained. Epidemiological studies have demonstrated that chronic mental stress in modern lifestyle is closely linked to the incidence of hypertension, cardiovascular disease, metabolic syndrome (MetS), and diabetes mellitus [1]. Accumulating evidence has demonstrated associations of disturbed psychophysiological responses with sub-clinical measures of atherosclerosis, hypertension, and metabolic risk [2]. As the onset of diabetes is closely linked to cardiovascular complications in hypertensive patients, stress-related disorders would be a potential therapeutic target in hypertensive patients. Stress activates the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis to alternate systemic hormonal and immune responses [3], resulting in negative health effects on glucose metabolism, leading to the onset of type 2 diabetes [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
