| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 96 === Background: Obesity has been regarded as a major risk factor for type 2 diabetes. In the adipocytes of obese subjects, pathologic changes lead to insulin resistance and cause diabetes. Many large clinical outcome trials have shown blockade of the rennin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) reduces the incidence of type 2 diabetes. The aim of our study is to determine the effects of RAS blockers on adipocyte differentiation and adipokine secretion.
Material and Method: The 3T3-L1 preadipocytes were used for cell culture and divided into Control group (no induction), Induction group，Induction plus ACEI or AT1R blocker or AT2R blocker. We described the state of adipocyte differentiation and fat accumulation. Oil-red O stain for cell staining, real-time PCR for mRNA analysis, and Western blot for protein analysis were performed.
Results: We found that as 3T3-L1 adipocytes differentiate, the cells enlarge with fat accumulation. The expressions of adipokine mRNA increased and so did angiotensinogen mRNA. AT1R mRNA was down-regulated. Expressions of ACE mRNA and AT2R mRNA reached the peak at day 2 of adipocyte differentiation. Additions of ACEI, AT1R blocker, or AT2R blocker changed the extents of adipocyte differentiation and fat accumulation with down-regulation of adipokine secretions. Besides, AT1R blocker and AT2R blocker but not ACEI restored the phosphorylation of IRS-1 and Akt proteins.
Discussion: ACEI might modulate adipocyte differentiations via mechanisms other than the IRS-1 and Akt pathways. AT1R blocker and AT2R blocker improved insulin signaling by restoring IRS-1 and Akt phosphorylation. The two receptors might have different ways of modulation, either to increase receptor activity (AT1R) or to increase mRNA expression (AT2R), which were blocked by its blockers to improve insulin resistance. Our results is the rationale that RAS blockers decrease the incidence of diabetes, which may be applied clinically to treat or even prevent obesity and its realted complications.
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