Effect of Irbesartan on Chemerin in the Renal Tissues of Diabetic Rats.

BACKGROUND/AIMS: Chemerin was introduced as a novel adipokine that plays a crucial role in insulin signaling and diabetic nephropathy. Serum chemerin levels are significantly elevated in type 2 diabetes patients with macroalbuminuria. However, the underlying mechanisms remain unclear. We conducted a preliminary investigation of the effects of the renin-angiotensin system (RAS) on chemerin expression in streptozotocin-induced diabetic rats. METHODS: Streptozotocin-induced diabetic rats were randomized into control, diabetic, and irbesartan-treated groups. Real-time polymerase chain reaction was used to detect mRNA expression of chemerin, angiotensin II type 1a receptor (AT1a), angiotensin II type 1b receptor (AT1b) and angiotensin II type 2 receptor (AT2). Immunohistochemical staining was used to detect chemerin in renal tissues. RESULTS: Expression levels of chemerin in renal tissues were significantly elevated in the diabetic group compared to the control group. In the irbesartan-treated group, chemerin expression levels and RAS-related protein levels (i.e. AT1a and AT1b) were markedly decreased compared to the diabetic group. Irbesartan treatment reduced chemerin overexpression and RAS-related protein levels in diabetic rats (i.e. AT1a and AT1b). CONCLUSION: Irbesartan may inhibit intrarenal RAS in diabetic rats, which may affect the expression of chemerin in the kidneys; however, the precise underlying mechanism remains to be determined.

Damage to vascular endothelial cells by high insulin levels is associated with increased expression of ChemR23, and attenuated by PPAR-gamma agonist, rosiglitazone.

OBJECTIVE: This study investigated the effect of different insulin concentrations on the activity of vascular endothelial cells (VECs), and the role of PPARγ activator rosiglitazone (RGZ) on the expression of the chemerin receptor, ChemR23, in insulin-treated human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was determined in HUVECs treated with different insulin concentrations. Immunofluorescence staining was used to detect ChemR23 expression in insulin-treated HUVECs. Western blot assays were used to evaluate ChemR23 and PPARγ protein expression in insulin-treated HUVECs after pretreatment with PPARγ activator (RGZ) or inhibitor (GW9662). RESULTS: High insulin concentrations significantly inhibited HUVEC cell viability compared to low insulin concentrations, and this inhibition was attenuated by pretreatment with RGZ. High concentrations of insulin caused a significant upregulation of ChemR23 and a significant downregulation of PPARγ. These effects were attenuated by RGZ pretreatment, while PPARγ antagonist, GW9662 reversed this attenuation. CONCLUSION: ChemR23 upregulation may play a role in VEC damage caused by high concentrations of insulin. The protective effect of PPARγ activation in VECs may be mediated via ChemR23 downregulation.