Dipeptidyl peptidase-4 (DPP-4): Localization and activity in human and rodent islets

• Islet DPP-4 is expressed mainly in α-cells in pig and human and β-cells in rodents.
• Active DPP-4 is expressed in INS-1 832/13 cells.
• DPP-4 activity was not changed by high glucose in isolated islets from mice and humans.
• Islet DPP-4 activity was robust when cultured with incretin hormones and insulin.
• Islet DPP-4 localization is similar in DIRKO mice and wild type mice.

Dipeptidyl peptidase 4 (DPP-4) was recently found to be expressed in human and mouse islets with different expression patterns. However, whether species-dependent expression pattern is a generalized phenomenon and whether islet DPP-4 activity is regulated are not known. This study was conducted to investigate DPP-4 localization in several different species, and to examine the impact of glucose, incretin hormones, and insulin on islet DPP-4 activity. It was shown by immuofluorescent staining that there were two distinct species-specific expression patterns of islet DPP-4. The enzyme was expressed exclusively in α-cells in human and pig islets, but primarily in β-cells in mouse and rat islets. INS-1 832/13 cells also expressed DPP-4, and inhibition of DPP-4 enhanced insulin secretion in the presence of glucagon-like peptide-1 (GLP-1) in the cells. DPP-4 activity was remarkably robust when cultured with high glucose, incretin hormones, and insulin in mouse and human islets as well as INS-1 832/13 cells and islet DPP-4 activity and expression pattern was not altered in double incretin receptor knockout mice, compared to wild type mice. We conclude that islet DPP-4 is species-specifically expressed in α-cell and β-cell dominant patterns in several species and both patterns remained robust in enzyme activity during short-term metabolic challenge.