This research study will examine brain glucose metabolism after an overnight fast to determine the effect of exenatide on brain glucose metabolism and lipid metabolism.

This study will elucidate if exenatide has an effect on brain glucose metabolism. This will be accomplished by measuring the rate of glucose binding in various brain regions by Positron Emission Tomography (PET) after glucose load with exenatide injection and compare it with placebo injection measured in the same subject. The changes will be compared with peripheral and hepatic glucose metabolism and lipolysis.

Inclusion Criteria:

1. Males age 18-65 years old

2. Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2

3. 2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes.

4. Patients must have BMI of 25-40 kg/m2

5. Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study.

6. Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.

7. Patients must have the following laboratory values:

   • Hematocrit ≥ 34 vol%
   • Serum creatinine* ≤ 1.5 mg/dl in males and
   • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT): ≤ 2.5 times upper limit of normal
   • Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT): ≤ 2.5 times upper limit of normal
   • Alkaline phosphatase ≤ 2.5 times upper limit of normal
   • If serum creatinine is ≤ 1.5 mg/dl in males, the PI can grant an exception and not exclude the patient if the Glomerular filtration rate (GFR) is >70 ml/min

Exclusion Criteria:

Patients are excluded from participation in the study if they meet any of the following criteria:

1. Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease)
2. Patients with BMI over 40 and under 25
3. Patient with age below 18 yrs and over 65 yrs
4. Female subjects
5. Patients with type 1 diabetes
6. Patients treated for type 2 diabetes
7. Subjects with normal glucose tolerance (NGT)

We studied male subjects with impaired fasting glucose or newly diagnosed type 2 diabetes.

Our study has several potential limitations. It included only men. During OGTT it is difficult to evaluate the separate contributions of glucose and insulin.