Laboratory of Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, Sichuan, 611130, China.
Metab Brain Dis. 2018 Oct;33(5):1483-1492. doi: 10.1007/s11011-018-0255-x. Epub 2018 Jun 11.
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.
下丘脑-垂体-肾上腺 (HPA) 轴作为能量代谢的关键调节剂，在糖尿病中发挥着重要作用。内源性大麻素系统 (eCBs) 参与神经元功能，并且根据大量报道，大麻素受体几乎在下丘脑的所有区域都有表达。然而，很少有数据研究 2 型糖尿病中 eCBs 和 HPA 轴的变化。在这项研究中，观察了 5 只糖尿病猕猴、5 只糖尿病前期猕猴和 5 只健康猕猴。在本研究中，我们广泛检测到糖尿病前期和显性糖尿病猴的室旁核 (PVN) 和神经垂体细胞肿胀和坏死。垂体中的促肾上腺皮质激素、肾上腺中的促肾上腺皮质激素受体和 11β-羟类固醇脱氢酶均从健康到显性糖尿病过度分泌和表达。同时，随着糖尿病的进展，肾上腺中的皮质醇浓度增加。可以得出结论，HPA 轴的功能亢进存在于 2 型糖尿病的发病机制中。然而，我们还发现 PVN 中促肾上腺皮质激素释放激素和糖皮质激素受体的表达和分泌减弱。糖尿病前期猕猴垂体中促肾上腺皮质激素释放激素受体 1 的表达减少，但显性糖尿病猕猴的表达增加。PVN 中大麻素受体 1 的下调和单甘油酯脂肪酶和脂肪酸酰胺水解酶的上调参与了 2 型糖尿病的发病机制。总之，我们可以得出结论，内源性大麻素水解酶和大麻素受体的变化可能表明 eCBs 下调的影响。可以假设，从健康到显性糖尿病的 HPA 轴的过度功能是由于 eCBs 的破坏抑制。然而，需要进一步探索 eCBs 对 HPA 轴的调节机制。
