Study desgin: Twenty healthy adults, age 21-55, will be recruited for this study. This is a randomized, double-blind, placebo-controlled cross-over study. Each subject will serve as his/her own control and each person will have four different study visits spaced about 3 weeks apart. During each visit, they will receive one of the following medications (oral route) in random order:1)Roflumilast (Daliresp) 500 mcg + Placebo; 2) Sitagliptin (Januvia) 100 mg + Placebo;3)Roflumilast (Daliresp) 500 mcg + Sitagliptin (Januvia) 100 mg; 4)Placebo. A 10-hr mixed-meal test will be administered 1 hour after the medications and frequent blood-samplings will be done over 10 hours. Medical Relevance and Expected Outcome: Preliminary clinical data have shown that phosphodiesterase inhibitors improved glycemic control in type 2 diabetes, and pre-clinical animal data have shown that phosphodiesterase inhibitors enhanced GLP-1 secretion from L cells. The application of novel, pre-clinical findings to an understanding of human biology and pathobiology is of fundamental and critical importance. This study will give us a better understanding of the regulators of GLP-1 secretion in humans, and this new understanding may lead to new treatments for type 2 diabetes. We have finished recruitment and are in the process of data analysis.
