Exenatide upregulates gene expression of glucagon-like peptide-1 receptor and nerve growth factor in streptozotocin/nicotinamide-induced diabetic mice.

Abstract

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.