Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance

Autor: Tadashi Matsushita, Kyosuke Takeshita, Toyoaki Murohara, Shigeo Nakamura, Motoharu Hayashi, Emiko Nomura, Ryosuke Kikuchi, Koji Yamamoto, Takayuki Nakayama, Yasuhiro Uchida, Xian Wu Cheng
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Panniculitis
Physiology
medicine.medical_treatment
Peptide Hormones
Angiotensinogen
Adipose tissue
Tetrazoles
lcsh:Medicine
White adipose tissue
Pathology and Laboratory Medicine
Biochemistry
Renin-Angiotensin System
Antihypertensive Drug Therapy
Medicine and Health Sciences
Psychology
lcsh:Science
Immune Response
Chemokine CCL2
Multidisciplinary
biology
Pharmaceutics
Drugs
Cardiovascular Therapy
Antihypertensive Drugs
Adipose Tissue
Anatomy
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Research Article
medicine.medical_specialty
Adipose Tissue
White
Lipolysis
Immunology
Psychological Stress
Proinflammatory cytokine
Insulin resistance
Irbesartan
Signs and Symptoms
Drug Therapy
Adipokines
Stress
Physiological
Internal medicine
medicine
Animals
Inflammation
Pharmacology
Adiponectin
Endocrine Physiology
Dose-Response Relationship
Drug
Insulin
Biphenyl Compounds
lcsh:R
Biology and Life Sciences
medicine.disease
Hormones
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
Biological Tissue
biology.protein
lcsh:Q
Insulin Resistance
Angiotensin II Type 1 Receptor Blockers
GLUT4
Zdroj: PLoS ONE, Vol 9, Iss 12, p e116163 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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