The Role of Phosphodiesterase Inhibitors in Incretin Secretion

Background: The drug Roflumilast (Daliresp) is used to treat Chronic Obstructive Pulmonary Disease (COPD). COPD is a lung disease that makes it difficult to breathe. Studies have shown that this drug decreased the blood sugar of people with type 2 diabetes. Sitagliptin (Januvia) is a medication presently used to treat diabetes. Researchers think that both of these drugs may decrease blood sugar by causing an increase in the hormone GLP-1.This hormone is secreted in the small intestines and stomach and is also known as an incretin. Researchers want to study how these drugs affect blood sugar, insulin, and other hormones in the blood. Objectives: * To study the effects of Roflumilast (Daliresp) and Sitagliptin (Januvia) on blood sugar and insulin. * To better understand GLP-1 and other gut hormones. This may lead to new treatments for type 2 diabetes. Eligibility: * Healthy volunteers age 21 55. * Body Mass Index (BMI) less than 30 Design: -This study will require one screening visit and four study visits, scheduled about 3-weeks apart. Screening visit requires participants to arrive after fasting for 10 hours and have the following: * Medical history, physical exam, height, weight, blood pressure measurements and blood and urine tests. * A 2-hour oral glucose tolerance test (OGTT). Participants will drink an orange-flavored drink containing 75 grams of sugar (300 calories). A blood sample will be taken prior to drinking the beverage and 2-hours later. * An electrocardiogram (EKG) to measure the electrical activity of the heart. * Questionnaires about risk for depression or suicide. Study visits 1to 4: * Participants will arrive the evening prior and blood work will be done to confirm eligibility. They will not eat or drink anything except water starting at 8:00 p.m. * About 6:30 a.m. the following day, an I.V. (small plastic tube) will be placed in an arm vein and used to take 20 blood samples over a period of about 11 hours. * Participants will receive on