Aldosterone and Glucose Homeostasis

Determine the effect of aldosterone on how the body handles glucose (sugar).

Determine the effect of aldosterone on glucose metabolism in humans.

Eligibility Criteria:
Inclusion Criteria:

1. Ambulatory subjects, 18 to 70 years of age, inclusive
2. For female subjects, the following conditions must be met:

   a postmenopausal status for at least 1 year, or b status-post surgical sterilization, or c if of childbearing potential, utilization of adequate birth control and willingness to undergo urine beta-hcg testing prior to drug treatment and on every study day
3. Metabolic Syndrome as defined by the presence of \> 3 of the following:

a Systolic Blood Pressure \> 130 mm Hg OR Diastolic Blood Pressure \> 85 mm Hg. b Glucose Intolerance (Fasting Plasma Glucose \> 100 mg/dL) c Increased triglyceride level \> 150mg/dL (1.7mmol/L) d Decreased levels of HDL cholesterol For males, less than 40 mg/dL For females, less than 50 mg/dL e Waist circumference For males, greater than 40 inches (102 cm) For females, greater than 35 inches (89 cm).

Exclusion Criteria:

1. Previously diagnosed Type I Diabetes , or the use of anti-diabetic medication. Subjects with type II diabetes not on medication will be allowed to participate if fasting blood glucose is \<200mg/dL.
2. Prior allergies to medications used in the study protocol (e.g. L-arginine, potassium chloride).
3. Screening plasma potassium \<3.5 mmol/L or use of chronic potassium supplements for the treatment of hypokalemia
4. Use of hormone replacement therapy
5. If on statin therapy for hypercholesterolemia, a change in dose within the past 6 months.
6. Breast-feeding
7. Cardiovascular disease such as prior myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
8. Treatment with anticoagulants
9. History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack
10. History or presence of immunological or hematological disorders
11. Diagnosis of asthma requiring use of inhaled beta agonist \>1 time per week
12. Clinically significant gastrointestinal impairment that could interfere with drug absorption
13. Impaired hepatic function \[aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) \>2.0 x upper limit of normal range\]
14. Impaired renal function \[estimated glomerular filtration rate (eGFR) of \<60ml/min\] as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dl and age in years:
15. eGFR \<60 ml/min
16. Hematocrit \<35%
17. 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, such as arthritis treated with non-steroidal antiinflammatory drugs
18. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
19. Treatment with lithium salts
20. History of alcohol or drug abuse
21. Treatment with any investigational drug in the 1 month preceding the study
22. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
23. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study