Chronic intermittent hypoxia leads to insulin resistance and impaired glucose tolerance through dysregulation of adipokines in non-obese rats.
OBJECTIVE
The aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms.


METHODS
An established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7-21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Glucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia.


CONCLUSIONS
These results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Cuiping
C
Fu
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. jiang_liyan@126.com.
Liyan
L
Jiang
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Fen
F
Zhu
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Zilong
Z
Liu
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Wenjing
W
Li
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Hong
H
Jiang
Division of Endocrinology, Hua Shan Hospital, Fudan University, Shanghai, China. dryehongying@hotmail.com.
Hongying
H
Ye
Stanford University Sleep Clinic and Center for Human Sleep Research, Redwood City, CA, USA. clete@stanford.edu.
Clete A
CA
Kushida
Department of Respiratory Medicine, Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China. lsq18616880856@163.com.|Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Fenglin Road 180, Xuhui District, Shanghai, 200032, People's Republic of China. lsq18616880856@163.com.
Shanqun
S
Li
D054392:Adipokines / Q000502:physiology*; D000273:Adipose Tissue / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000860:Hypoxia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D012016:Reference Values
D054392:Adipokines; D001786:Blood Glucose; D007328:Insulin
Adipokine; Chronic intermittent hypoxia; Impaired glucose tolerance; Insulin resistance; Sleep apnea