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.