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

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.