Circadian misalignment alters insulin sensitivity during the light phase and shifts glucose tolerance rhythms in female mice

Autoři: Li-Xin Zhong aff001;  Xiao-Na Li aff001;  Guang-Yu Yang aff002;  Xia Zhang aff001;  Wen-Xue Li aff002;  Qian-Qian Zhang aff001;  Huan-Xin Pan aff001;  Hui-Hong Zhang aff003;  Meng-Ya Zhou aff003;  Yi-Ding Wang aff003;  Wei-Wei Zhang aff002;  Qian-Sheng Hu aff001;  Wei Zhu aff002;  Bo Zhang aff003
Působiště autorů: Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China aff001;  Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, China aff002;  Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Shift work and jet lag, characterized by circadian misalignment, can disrupt several physiological activities, but whether they affect the rhythm of glucose uptake and insulin sensitivity remain unclear. In the present study, female C57BL/6J mice were maintained for four weeks under the condition of 8-hour phase advance and delay every 3–4 days to mimic shift work. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were performed repeatedly at Zeitgeber time (ZT) 0, ZT6, ZT12, and ZT18. Glucose-stimulated insulin secretion (GSIS) test was performed at ZT6. We found that the average level of daily glucose tolerance did not decrease but the phase of glucose tolerance advanced by 2.27 hours and the amplitude attenuated by 20.4% in shift work mice. At ZT6, IPITT showed blood glucose at 30 min after insulin injection decreased faster in shift work mice (3.50±0.74mmol/L, 61.58±7.89%) than that in control mice (2.11±1.10mmol/L, 33.72±17.24%), but IPGTT and GSIS test showed no significant difference between the two groups. Food intake monitor showed that the feeding time of shift work mice continued to advance. Restricting feed to a fixed 12-hour period alleviated the increase of insulin sensitivity induced by shift-work. We also observed that an increase of blood glucose and liver glycogen at ZT0, as well as a phase advance of liver clock genes and some glucose metabolism-related genes such as forkhead box O1 (Foxo1) and peroxisome proliferator activated receptor alpha (Pparα) in shift work mice. Our results showed that light change-simulated shift work altered insulin sensitivity during the light phase and shifted glucose tolerance rhythms in female mice, suggesting a causal association between long-term shift work and type 2 diabetes.

Klíčová slova:

Blood plasma – Blood sugar – Circadian rhythms – Glucose – Glucose metabolism – Glucose tolerance – Glycogens – Insulin


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