Carvedilol prevents pancreatic β-cell damage and the development of type 1 diabetes in mice by the inhibition of proinflammatory cytokines, NF-κB, COX-2, iNOS and oxidative stress.
Inflammation is one of the main mechanisms of pancreatic β-cell damage and the development of type 1 diabetes (T1D). Carvedilol, a beta-adrenergic receptor blocker, has been demonstrated to have anti-inflammatory and antioxidant effects. The aim of this study was to investigate the protective effect of carvedilol against pancreatic β-cell damage and the development of T1D in an experimental model. T1D was induced in mice by multiple low-dose streptozotocin (STZ) injections. Diabetic mice were treated with carvedilol (15 and 20 mg/kg/day, orally) for 14 days. Results showed that blood glucose levels, diabetes incidence, body weight loss and insulitis in the pancreatic tissue were significantly reduced in mice treated with carvedilol. Treatment of mice with carvedilol significantly increased the levels of antioxidants glutathione (GSH), superoxide dismutase (SOD), and catalase and decreased the levels of malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) in the pancreatic tissue as compared with those in the STZ-induced diabetic mice. Carvedilol decreased the expression of nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as important modulators of inflammation and β-cell damage in the pancreatic tissue. In addition, carvedilol significantly reduced the levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 IL-12, IL-17, interferon (IFN)-γ and chemokine MCP-1, while increased the anti-inflammatory cytokine IL-10 in the pancreatic tissue. In conclusion, these findings suggest that carvedilol is able to prevent pancreatic β-cell damage and the development of T1D in mice by the inhibition of inflammatory and oxidative mediators.