Liraglutide alters DPP4 in the circumvallate papillae of type 2 diabetic rats

Abstract

Liraglutide, a human glucagon-like peptide (GLP1) analog that partially inhibits dipeptidyl-peptidase 4 (DPP4), can decrease glucose levels and suppress appetite in patients with type 2 diabetes (T2DM). GLP1 and its receptor (GLP1R) also exist in the taste buds of rodents and regulate taste sensitivity. DPP4, a protease, functions in homeostasis of blood glucose, lipids, and body weight. Interactions among GLP1, GLP1R, and DPP4 likely affect taste and food-intake behavior. The aim of the present study was to investigate DPP4 expression in the taste buds of the circumvallate papillae (CV) in T2DM rats, and determine the effects of liraglutide treatment. Rats were divided into diabetic control (T2DM-C), normal control (NC), and liraglutide-treated diabetic (T2DM+LIR) groups. DPP4 localization and gene expression levels were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-qPCR), respectively. DPP4 immunoreactive cells were localized in the taste buds of the rat CV. RT-qPCR showed significantly higher expression of Dpp4 mRNA in both the taste buds and hypothalamus of T2DM-C rats compared with NC rats. However, in the T2DM+LIR group, Dpp4 expression differed between the taste buds and hypothalamus, with significantly higher and lower levels compared with the T2DM-C group, respectively. Dpp4 mRNA expression is increased in the taste buds of the CV of T2DM rats. Liraglutide simultaneously upregulated (taste buds) and downregulated (hypothalamus) Dpp4 expression in T2DM rats. Therefore, DPP4 may be closely associated with the anorexigenic signaling and weight loss induced by the treatment of liraglutide in type 2 diabetic patients.