Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway.
Obstructive sleep apnea (OSA) is a breathing disorder during sleep, with a most prominent character of chronic intermittent hypoxia (CIH), which induces the generation of reactive oxygen species (ROS) that damages multiple tissues and causes metabolic disorders. In this study, we established a rat model of varying OSA with different grades 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 pancreatic tissue, and caused pancreatic tissue lesions and cell apoptosis in a dose-dependent manner. Moreover, CIH promoted the production of tumor necrosis factor (TNF)-α, 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, depending on the O2concentration. In summary, CIH disturbed insulin secretion, and caused inflammation, lesions, and cell apoptosis in pancreatic tissue via the MAPK signaling pathway, which may be of great significance for clinical treatment of OSA and type 2 diabetes mellitus (T2DM).
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.|b Department of Epidemiology and Biostatistics, School of Public Health, Kunming Medical University, Kunming, Yunnan 650500, People's Republic of China.
Yeying
Y
Wang
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Bing
B
Hai
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Xiaoqun
X
Niu
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Li
L
Ai
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Yu
Y
Cao
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Ran
R
Li
a Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, People's Republic of China.
Yongxia
Y
Li
D000818:Animals; D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000473:pathology; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D010179:Pancreas / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007328:Insulin; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
MAPK; apnée obstructive du sommeil; chronic intermittent hypoxia; hypoxie intermittente chronique; insulin; insuline; obstructive sleep apnea; pancreas; pancréas