Gumuslu Esen, Cine Naci, Ertan Merve, Mutlu Oguz, Komsuoglu Celikyurt Ipek, Ulak Guner
Department of Medical Genetics, Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
Fundam Clin Pharmacol. 2018 Apr;32(2):174-180. doi: 10.1111/fcp.12329. Epub 2017 Nov 20.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including the brain. The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex, and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer's disease to diabetic neuropathies. Exenatide, a potent and selective agonist for the GLP-1 receptor, is currently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to assess the effect of chronic exenatide treatment on the hippocampal gene expression levels of GLP-1 receptor and NGF in diabetic mice. The effects of chronic exenatide treatment (0.1 μg/kg, s.c., twice daily for 2 weeks) on GLP-1 receptor and NGF gene expression levels in the hippocampus of streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice were assessed by quantitative real-time polymerase chain reaction (RT-PCR). The results of this study revealed that hippocampal gene expression of GLP-1 receptor and NGF were downregulated in diabetic mice. Importantly, a significant increase in the gene expression level of GLP-1 receptor and NGF was determined after 2 weeks of exenatide administration. Increased gene expression level of GLP-1 receptor and NGF may underlie the beneficial action of exenatide in STZ/NA-induced diabetes.
胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素，对胰岛素释放具有调节作用。GLP-1及其受体在包括大脑在内的全身广泛表达。GLP-1受体的表达在海马体、新皮层和小脑中的大神经元中非常特异。刺激GLP-1受体可增强2型糖尿病患者的葡萄糖依赖性胰岛素分泌并降低血糖。神经营养因子的脂肪生物学研究主要集中在神经生长因子（NGF），它是脂肪源性神经营养因子的一个例子。营养因子信号传导受损可能是从阿尔茨海默病到糖尿病神经病变等神经退行性疾病的基础。艾塞那肽是一种强效且选择性的GLP-1受体激动剂，目前已被批准用于治疗2型糖尿病。本研究的目的是评估长期给予艾塞那肽对糖尿病小鼠海马体中GLP-1受体和NGF基因表达水平的影响。通过定量实时聚合酶链反应（RT-PCR）评估长期给予艾塞那肽（0.1μg/kg，皮下注射，每日两次，共2周）对链脲佐菌素/烟酰胺（STZ-NA）诱导的糖尿病小鼠海马体中GLP-1受体和NGF基因表达水平的影响。本研究结果显示，糖尿病小鼠海马体中GLP-1受体和NGF的基因表达下调。重要的是，给予艾塞那肽2周后，GLP-1受体和NGF的基因表达水平显著增加。GLP-1受体和NGF基因表达水平的增加可能是艾塞那肽对STZ/NA诱导的糖尿病产生有益作用的基础。
