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PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin
Ronald Clasen1, Michael Schupp, Anna Foryst-Ludwig
1Center for Cardiovascular Research, Institut für Pharmakologie und Toxikologie, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany. .
Hypertension (Dallas, Tex. : 1979)
|June 9, 2005
Summary
Angiotensin type-1 receptor blockers (ARBs) increase adiponectin, a protein that improves insulin sensitivity. This effect is mediated by peroxisome proliferator-activated receptor gamma (PPARγ) activation, offering new insights into ARB antidiabetic mechanisms.
Area of Science:
- Endocrinology
- Metabolic Syndrome
- Pharmacology
Background:
- Adiponectin, an adipose-specific protein, enhances insulin sensitivity.
- Angiotensin type-1 receptor blockers (ARBs) reduce type 2 diabetes mellitus incidence via unknown mechanisms.
- Understanding ARB antidiabetic pathways is crucial for metabolic disease management.
Purpose of the Study:
- To investigate the regulation of adiponectin by angiotensin II (Ang II) and ARBs.
- To elucidate the molecular mechanisms underlying ARB-mediated improvements in insulin sensitivity.
- To identify novel antidiabetic mechanisms of ARBs involving adiponectin.
Main Methods:
- Murine 3T3-L1 adipocytes and obese Zucker rats were used to study adiponectin regulation.
- Experiments involved Ang II stimulation, ARB treatment, and blockade of AT2R and PPARγ.
- Adiponectin protein and mRNA levels were quantified; insulin sensitivity was assessed in vivo.
Main Results:
- Angiotensin II (Ang II) stimulated adiponectin, an effect inhibited by AT2R blockade and enhanced by irbesartan.
- Irbesartan and telmisartan, but not eprosartan, upregulated adiponectin protein expression.
- PPARγ activation was essential for irbesartan-induced adiponectin expression, which occurred post-transcriptionally.
- Irbesartan treatment improved insulin sensitivity and prevented adiponectin depletion in obese rats.
Conclusions:
- Certain ARBs, like irbesartan and telmisartan, induce adiponectin in adipocytes through PPARγ activation.
- This ARB-mediated adiponectin stimulation represents a novel, post-transcriptional mechanism contributing to improved insulin sensitivity.
- The findings reveal a new therapeutic avenue for managing type 2 diabetes mellitus.