Soluble Epoxide Hydrolase Inhibition and Insulin Resistance

Inclusion Criteria: 1. Men and women, 2. Age 21 to 50 years, and 3. Pre-diabetes as defined by 1. Fasting plasma glucose 100-125 mg/dL, or 2. Two-hour plasma glucose 140-199 mg/dL, or 3. HbA1c 5.7-6.4% 4. BMI ≥ 30 kg/m2, inclusive 5. For female subjects, the following conditions must be met: 1. Postmenopausal status for at least one year, or 2. Status-post surgical sterilization, or 3. If of childbearing potential, utilization of adequate birth control and willingness to undergo serum β-hcg testing prior to drug treatment and on every study day. Exclusion Criteria: 1. Diabetes type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, a HbA1c \>6.4%, or the use of anti-diabetic medication 2. Subjects who have participated in a weight-reduction program during the last six month or whose weight has increased or decreased more than two kg over the preceding six months 3. Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control 4. Use of spironolactone 5. Pregnancy or breast-feeding 6. Any history of smoking 7. Any history of cancer including skin cancer, any history of a precancerous lesion, abnormal PSA, or lack of screening adherent to American Cancer Society Guidelines for the Early Detection of Cancer 8. Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep-vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy 9. Abnormal corrected QT interval on screening ECG (QTc). 10. Treatment with anticoagulants 11. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack 12. History or presence of immunological or hematological disorders 13. Diagnosis of asthma requiring regular inhaler use 14. Clinically significant gastrointestinal impairment that could interfere with drug absorption 15. Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>3.0 x upper limit of normal range) 16. History of gastrointestinal bleed 17. Estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73 m2 or with an albumin-to-creatinine ratio (UACR) \>300µg/mg, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female) 18. Hematocrit \<35% 19. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult 20. Treatment with chronic systemic glucocorticoid therapy 21. Treatment with lithium salts 22. History of alcohol or drug abuse 23. Treatment with any investigational drug in the month preceding the study 24. Mental conditions rendering a subject unable to understand the nature, scope, and possible consequences of the study 25. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study