Abstract

Pancreatic alpha cells secrete glucagon-like peptide 1 (GLP-1), the production of which is enhanced by the chemokine stromal derived factor 1 (SDF-1). Since SDF-1, like GLP-1, is a substrate of dipeptidyl peptidase-4 (DPP-4), we examined whether dual therapy with SDF-1 and a DPP-4 inhibitor would preserve beta cell function and mass in diabetes. Diabetes was induced by daily injections of streptozotocin for 5 days. One diabetic group was treated with daily injections of SDF-1 alpha or vehicle for 5 days. These mice were concurrently treated with either the DPP-4 inhibitor vildagliptin or vehicle and they remained on vildagliptin or vehicle for an additional 3 weeks. Glucose clearance and beta cell function was evaluated from glucose and insulin data during OGTTs performed after 0, 2 and 4 weeks of treatment. Beta cell mass was determined histologically. Body weight did not differ between diabetic groups during the study. OGTT data showed that diabetic mice treated with SDF-1 alpha in combination with vildagliptin had increased glucose clearance which was not observed with vildagliptin alone. In contrast, vildagliptin alone enhanced beta cell function with no further enhancement by the combination with SDF-1 alpha. Beta cell mass and islet GLP-1 content were not altered by the treatments. In conclusion, SDF-1 alpha and vildagliptin combination therapy improves glucose clearance in streptozotocin induced diabetes in the mouse by an effect which seems independent from enhanced beta cell function.

Keywords: Glucose; Insulin; GLP-1; SDF-1; DPP-4; Diabetes