Type 2 diabetes (TD2) is a sustained metabolic disorder, characterized by high blood glucose, insulin resistance (IR). Dipeptidyl peptidase-4 (DPP4) functions as an antigenic enzyme involved in hyperglycaemia, oxidative stress, and inflammation-associated IR. Therefore, association between DPP4 and TD2 warrants to be investigated.

In this study, blood samples of clinically diagnosed TD2 patients were harvested for biochemical tests. In addition, diabetic mice induced by high-fat diet (HFD) and single dose of streptozotocin (STZ) were used to assess the biological characteristics of DPP4 through biochemical and enzyme-linked immunosorbent assay (ELISA) tests, immunofluorescence staining, and western blot assay.

Compared to controls, the clinical data of patients with TD2 resulted in increased contents of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), homeostatic model assessment (HOMA)-IR, blood lipids of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and interleukin 6 (IL6) in plasma samples (p < 0.05). Notably, blood levels of DPP4 in TD2 patients were increased significantly in comparison to that in non-diabetic adults (p < 0.01). In animal study, diabetic mice showed increased levels of glucose, insulin, lipids, DPP4 activity in sera. Visibly, hepatocellular DPP4 expression was up-regulated in diabetic mice. Interestingly, DPP4 inhibitor-treated mice showed significantly reduced DPP4 expression in serum (p < 0.01), and lowered DPP4-positive cells and protein content in the liver were observed when compared to those in diabetic mice (p < 0.01).

Collectively, these findings reveal that DPP4 biomolecule may be positively associated with TD2 development, and the underlying mechanism may be attributed to activation of DPP4 expression in liver cells.