Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via MAPK signaling pathway

Abstract

Obstructive sleep apnea (OSA) is a breath disorder during sleep with a most prominent character of chronic intermittent hypoxia (CIH), inducing the generation of reactive oxygen species (ROS) to damage multiple tissues and cause metabolism disorders. In this study, we established rat varying OSA model by graded concentration of CIH (12.5% O2, 10% O2, 7.5%O2 and 5% O2) for 12 weeks, and found that CIH stimulated insulin secretion, reduced the insulin/proinsulin ratio in the pancreatic tissue, and caused pancreatic tissue lesions and cells apoptosis in a dose-dependent manner. Moreover, CIH promoted the production of tumor necrosis factor (TNF)-ι, Interleukin (IL)-1β and IL-6, and activated mitogen-activated protein kinase (MAPK) family members, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and P38 relying on the O2 concentration. In summary, CIH disturbed insulin secretion, caused inflammation, lesion and cell apoptosis in pancreatic tissue via MAPK signaling pathway, which may be of great significance for clinical treatment of OSA and type 2 diabetes mellitus (T2DM).