Long-lasting expression of HO-1 delays progression of type I diabetes in NOD mice.

Overview

Heme oxygenase-1 (HO-1) is crucial in regulating oxidative injury. The present study was designed to assess whether HO-1 upregulation by cobalt protoporphyrin IX (CoPP) moderates or prevents the diabetic state in non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes (T1D). HO-1 expression and HO activity were upregulated in the pancreas by the intermittent administration of CoPP. This was associated with decreases in blood glucose and pancreatic O2-, but increased pAKT and BcL-XL and cell survival. A considerable number of beta cells were preserved in the islets of CoPP-treated NOD mice, while none were found in untreated diabetic mice. The number of CD11c+ dendritic cells was decreased in the pancreas of CoPP-treated NOD mice (p < 0.05). These novel findings provide a link between the increase in HO-1 and a decrease in infiltrated CD11c+ dendritic cells, and suggest that induction of HO-1 activity can be used to enhance cell survival and moderate the diabetic state in T1D.