Pancreatic effects of diesel exhaust particles in mice with type 1 diabetes mellitus

Abstract

Background/aims: Epidemiologically, diabetics are more prone to the adverse health effects of particulate air pollution than healthy individuals. We recently demonstrated an increased cardiovascular and respiratory susceptibility to diesel exhaust particles (DEP) in mice with type 1 diabetes. However, the pancreatic effects of DEP in healthy and diabetic mice are unknown.

Methods: Presently, we evaluated the pancreatic impact of DEP in healthy mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, mice were intratracheally instilled (i.t.) with either DEP (0.4 mg/kg) or saline, and several histological and biochemical endpoints were measured 24 h thereafter.

Results: Neither the histology nor the stain for apoptosis in the pancreatic islets and exocrine glands were affected by DEP. In diabetic mice exposed to saline, the islet cells showed cellular vacuolation and apoptotic islet cells (71.6 ± 2.6%). In diabetic mice exposed to DEP, a more marked decrease in the size and number of islet cells with cellular vacuolation along with a significant increase of apoptotic islet cells (79.1 ± 1.7 %, P<0.05) were observed. In diabetic mice, DEP increased significantly pancreatic amylase activity and markers of oxidative stress including 8-isoprostane, superoxide dismutase and reduced glutathione compared with either diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Staining for inducible nitric oxide synthase (iNOS) in healthy mice exposed to either saline or DEP showed no staining in either pancreatic islets cells or acini. In saline-treated diabetic mice, a mild cytoplasmic staining for iNOS in some pancreatic islet cells was observed. Notably, in diabetic mice exposed to DEP, a marked cytoplasmic staining for iNOS in most pancreatic islet cells and some acinar cells was seen.

Conclusion: We conclude that DEP caused detrimental effects on the pancreas of diabetic mice, and that oxidative stress is responsible, at least partially, for the observed effects.