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Endocannabinoid hydrolase and cannabinoid receptor 1 are involved in the regulation of hypothalamus-pituitary-adrenal axis in type 2 diabetes

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Abstract

Hypothalamus-pituitary-adrenal (HPA) axis, as the key moderator in energy metabolism, plays an important role in diabetes. The endogenous cannabinoid system (eCBs) involves in neuronal functions, and simultaneously cannabinoid receptors are almost expressed in all regions of the hypothalamus according to a spate of reports. However, few data investigate the changes of eCBs and HPA axis in type 2 diabetes. In this study, five diabetes mellitus rhesus monkeys, five prediabetes rhesus monkeys and five healthy rhesus monkeys were observed. In the present study, we detected cell swelling and necrosis extensively in the paraventricular nucleus (PVN) and neurohypophysis in prediabetes and overt diabetes monkeys. The adrenocorticotropic hormone in the pituitary gland, adrenocorticotropic hormone receptor, and 11β-hydroxysteroid dehydrogenase in the adrenal gland were all hyper-secreted and expressed from healthy to overt diabetes. Meanwhile, the cortisol concentration in the adrenal gland was increased along with the progress of diabetes. It could be concluded that hyperfunction of the HPA axis exists in the type 2 Diabetes pathogenesis. However, we also found a weakened expression and secretion of corticotrophin releasing hormone and glucocorticoids receptor in PVN. The expression of corticotropin releasing hormone receptor 1 in pituitary gland decreased in prediabetes monkeys, but increased in overt diabetes monkeys. The downregulation of cannabinoid receptor 1 and upregulation of monoglycerol lipase and fatty acid amide hydrolase in PVN was involved in the pathogenesis of type 2 diabetes. Collectively, we can conclude that changes in endocannabinoid hydrolase and cannabinoid receptor might indicate the effect of downregulation of eCBs. It can be assumed that hyper-function of the HPA axis from healthy to overt diabetes is due to the undermining inhibition of eCBs. However, the regulatory mechanism of eCBs targets on the HPA axis need to be further explored.

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Acknowledgements

The work is supported by the National Key Scientific Instrument and Equipment Development Project of China (2013YQ49085906), the National Key Technology R&D Program of the Ministry of Science and Technology (2014BAI03B01).

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Author notes

  1. Qihui Luo and Shanshan Chen contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China

    Qihui Luo, Shanshan Chen, Juan Deng, Liangqin Shi, Chao Huang, Anchun Cheng, Wentao Liu, Jing Fang, Li Tang, Yi Geng & Zhengli Chen

  2. Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya’an, Sichuan, 611130, China

    Qihui Luo, Shanshan Chen, Juan Deng, Liangqin Shi, Chao Huang, Anchun Cheng, Jing Fang, Li Tang, Yi Geng & Zhengli Chen

  3. Animal Disease Control and Prevention Centres, Yilong, Sichuan, 637676, China

    Shanshan Chen & Wentao Liu

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  1. Qihui Luo
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  2. Shanshan Chen
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  3. Juan Deng
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  11. Zhengli Chen
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Correspondence to Zhengli Chen.

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Luo, Q., Chen, S., Deng, J. et al. Endocannabinoid hydrolase and cannabinoid receptor 1 are involved in the regulation of hypothalamus-pituitary-adrenal axis in type 2 diabetes. Metab Brain Dis 33, 1483–1492 (2018). https://doi.org/10.1007/s11011-018-0255-x

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  • DOI: https://doi.org/10.1007/s11011-018-0255-x

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