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

• Published in: Metabolic brain disease Vol. 33; no. 5; pp. 1483 - 1492
• Main Authors: Luo, Qihui, Chen, Shanshan, Deng, Juan, Shi, Liangqin, Huang, Chao, Cheng, Anchun, Liu, Wentao, Fang, Jing, Tang, Li, Geng, Yi, Chen, Zhengli
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2018; Springer Nature B.V
• Subjects: 11β-Hydroxysteroid dehydrogenase; Adrenal glands; Adrenal Glands - metabolism; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - metabolism; Amidohydrolases - metabolism; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cannabinoid receptors; Cell size; Corticotropin-releasing hormone; Cortisol; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Endocannabinoid system; Endocannabinoids - metabolism; Energy metabolism; Fatty acids; Fatty-acid amide hydrolase; Gene Expression Regulation; Glucocorticoids; Hydrocortisone - metabolism; Hydrolase; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - metabolism; Hypothalamus; Hypothalamus - metabolism; Lipase; Macaca mulatta; Male; Metabolic Diseases; Metabolism; Monkeys; Necrosis; Neurology; Neurosciences; Nuclei (cytology); Oncology; Original Article; Paraventricular nucleus; Pathogenesis; Pituitary; Pituitary (posterior); Pituitary gland; Pituitary-Adrenal System - metabolism; Receptor, Cannabinoid, CB1 - metabolism; Receptors; Regulatory mechanisms (biology); Secretion; Rhesus monkey; Hypothalamus-pituitary-adrenal axis; Endocannabinoid hydrolase; Cannabinoid receptor 1; Type 2 diabetes mellitus
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-018-0255-x

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.