Ouedraogo Raogo, Näslund Erik, Kirchgessner Annette L
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.
Diabetes. 2003 Jan;52(1):111-7. doi: 10.2337/diabetes.52.1.111.
Orexins (hypocretins) are novel neuropeptides that appear to play a role in the regulation of energy balances. Orexin-A (OXA) increases food intake in rodents, and fasting activates OXA neurons in both the lateral hypothalamic area and gut. OXA is also found in the endocrine pancreas; however, little is known about its release or functional significance. In this study, we show that depolarizing stimuli evoke the release of OXA from rat pancreatic islets in a calcium-dependent manner. Moreover, OXA release is stimulated by low glucose (2.8 mmol/l), similar to glucagon secretion, and inhibited by high glucose (16.7 mmol/l). Fasting increases plasma OXA, supporting the idea that orexin is released in response to hypoglycemia. Cells that secrete glucagon and insulin contain OXA and both cell types express orexin receptors. OXA increases glucagon secretion and decreases glucose-stimulated insulin release from isolated islets. OXA infusion increases plasma glucagon and glucose levels and decreases plasma insulin in fasted rats. We conclude that orexin-containing islet cells, like those in the brain and gut, are glucosensitive and part of a network of glucose "sensing" cells that becomes activated when blood glucose levels fall. OXA may modulate islet hormone secretion to maintain blood glucose levels during fasting.
食欲素（下丘脑泌素）是一类新型神经肽，似乎在能量平衡调节中发挥作用。食欲素A（OXA）可增加啮齿动物的食物摄入量，禁食可激活下丘脑外侧区和肠道中的OXA神经元。内分泌胰腺中也发现了OXA；然而，对其释放或功能意义知之甚少。在本研究中，我们发现去极化刺激以钙依赖的方式诱发大鼠胰岛释放OXA。此外，低葡萄糖（2.8 mmol/L）刺激OXA释放，这与胰高血糖素分泌类似，而高葡萄糖（16.7 mmol/L）则抑制OXA释放。禁食会增加血浆OXA水平，支持食欲素在低血糖反应时释放的观点。分泌胰高血糖素和胰岛素的细胞含有OXA，且这两种细胞类型均表达食欲素受体。OXA可增加胰高血糖素分泌，并减少分离胰岛的葡萄糖刺激的胰岛素释放。在禁食大鼠中，输注OXA会增加血浆胰高血糖素和葡萄糖水平，并降低血浆胰岛素水平。我们得出结论，含食欲素的胰岛细胞与大脑和肠道中的细胞一样，对葡萄糖敏感，是血糖“感知”细胞网络的一部分，当血糖水平下降时被激活。OXA可能调节胰岛激素分泌以在禁食期间维持血糖水平。
