Spetter Maartje S, Hallschmid Manfred
†Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
‡German Center for Diabetes Research (DZD), 72076 Tübingen, Germany.
Mol Pharm. 2015 Aug 3;12(8):2767-80. doi: 10.1021/acs.molpharmaceut.5b00047. Epub 2015 Apr 28.
Central nervous system control of metabolic function relies on the input of endocrine messengers from the periphery, including the pancreatic hormone insulin and the adipokine leptin. This concept primarily derives from experiments in animals where substances can be directly applied to the brain. A feasible approach to study the impact of peptidergic messengers on brain function in humans is the intranasal (IN) route of administration, which bypasses the blood-brain barrier and delivers neuropeptides to the brain compartment, but induces considerably less, if any, peripheral uptake than other administration modes. Experimental IN insulin administration has been extensively used to delineate the role of brain insulin signaling in the control of energy homeostasis, but also cognitive function in healthy humans. Clinical pilot studies have found beneficial effects of IN insulin in patients with memory deficits, suggesting that the IN delivery of this and other peptides bears some promise for new, selectively brain-targeted pharmaceutical approaches in the treatment of metabolic and cognitive disorders. More recently, experiments relying on the IN delivery of the hypothalamic hormone oxytocin, which is primarily known for its involvement in psychosocial processes, have provided evidence that oxytocin influences metabolic control in humans. The IN administration of leptin has been successfully tested in animal models but remains to be investigated in the human setting. We briefly summarize the literature on the IN administration of insulin, leptin, and oxytocin, with a particular focus on metabolic effects, and address limitations and perspectives of IN neuropeptide administration.
中枢神经系统对代谢功能的控制依赖于来自外周的内分泌信使的输入，包括胰腺激素胰岛素和脂肪因子瘦素。这一概念主要源于在动物身上进行的实验，在这些实验中，物质可以直接应用于大脑。研究肽能信使对人类大脑功能影响的一种可行方法是鼻内（IN）给药途径，该途径绕过血脑屏障，将神经肽输送到脑区，但与其他给药方式相比，其诱导的外周摄取（如果有的话）要少得多。实验性鼻内胰岛素给药已被广泛用于阐明脑胰岛素信号在能量稳态控制中的作用，以及在健康人类中的认知功能。临床初步研究发现鼻内胰岛素对记忆缺陷患者有有益影响，这表明这种肽和其他肽的鼻内给药在治疗代谢和认知障碍方面有望成为新的、具有选择性脑靶向性的药物治疗方法。最近，依赖于鼻内递送主要因其参与社会心理过程而闻名的下丘脑激素催产素的实验提供了证据，表明催产素会影响人类的代谢控制。瘦素的鼻内给药已在动物模型中成功测试，但仍有待在人体中进行研究。我们简要总结了关于胰岛素、瘦素和催产素鼻内给药的文献，特别关注代谢效应，并探讨鼻内神经肽给药的局限性和前景。
