Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects

Inclusion Criteria: 1. Age 40-65 years inclusive 2. Men and women 3. Able to provide written, informed consent 4. Weight stable (± 3 kg) during the 3 months prior to enrollment 5. BMI ≥ 30 kg/m2; body weight ≤ 106 kg 6. Resting blood pressure ≥ 110/60 mmHg and ≤ 150/100 mmHg Exclusion Criteria: 1. Known coronary artery disease, angina or heart failure 2. Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose \>125mg/dL) 3. Bleeding disorders 4. Hemoglobin level \< 12.5 g/dL for women; \< 13.0 g/dL for men 5. Acute or chronic infections 6. Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal) 7. Severe asthma or chronic obstructive pulmonary disease 8. Renal insufficiency (creatinine \> 1.6 mg/dL) 9. Prior bariatric surgery 10. Inflammatory bowel disease or malabsorption 11. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ) 12. Psychiatric or eating disorders 13. Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders 14. Active rheumatoid arthritis or other inflammatory rheumatic disorder 15. Pregnant or nursing women 16. Presence of clinically significant abnormalities on electrocardiogram 17. Smoking (within the last 3 months) 18. Known hypersensitivity to nesiritide or any of its excipients 19. Poor intravenous access 20. Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable), f) chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phenteramine or other weight loss or anorectic agents.