Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Int J Mol Sci. 2022 Jan 4;23(1):548. doi: 10.3390/ijms23010548.
The incretin system is an emerging new field that might provide valuable contributions to the research of both the pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the roles of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain, as well as on the levels of these incretins, insulin, and glucose via inhibition of the central incretin receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer's disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.
肠促胰岛素系统是一个新兴的领域，可能为糖尿病、肥胖症和神经退行性疾病的病理生理学和治疗策略的研究提供有价值的贡献。本研究旨在探讨中枢胰高血糖素样肽-1（GLP-1）和胃抑制多肽（GIP）对大脑细胞代谢和能量的作用，以及通过向健康大鼠和链脲佐菌素诱导的散发性阿尔茨海默病（sAD）大鼠模型的侧脑室给予相应拮抗剂抑制中枢肠促胰岛素受体后，这些肠促胰岛素、胰岛素和葡萄糖的水平。化学消融健康和患病动物的中枢 GIP 受体（GIPR）或 GLP-1 受体（GLP-1R）表明，肠促胰岛素在脑细胞能量和代谢中具有区域依赖性作用，并且中枢肠促胰岛素依赖性调节外周激素分泌，在 GIPR 抑制后更为明显，以及实验性 sAD 中 GLP-1 系统的失调。
