 Euglycemic Insulin Clamp with Muscle Biopsies. The degree of insulin resistance will be estimated with the euglycemic hyperinsulinemic clamp technique 23 using an insulin infusion rate 80 mUm2.min, as previously described 24. Briefly, one week after completion of the screening visit 2 Visit 3, patients will report to the Clinical Research Unit at 8:00 AM after a 10-12 hour overnight fast. Catheters will be inserted into a peripheral vein for infusion of all test substances and into a retrograde hand vein for blood sampling, which will be placed in a heated box 750 C. At time t -120 minutes, a percutaneous biopsy of the vastus lateralis muscle will be performed under local anesthesia as previously described 25. The subject then will be allowed to rest in bed for 60 minutes. At time t -30 min to 0 min baseline blood samples will be obtained. At time 0 min, insulin will be infused at 80 mUm2.min for 180 minutes to raise the plasma insulin concentration to approximately 120 μUml to examine peripheral tissue muscle sensitivity to insulin. During the insulin clamp, a small amount of blood 0.5 ml is withdrawn every 5 minutes from the arterialized venous blood heated box technique to determine plasma glucose concentration. When the plasma glucose concentration declines to 100 mgdl a variable infusion of 20 dextrose is appropriately adjusted to maintain the plasma glucose concentration constant at this level 5. The rate of exogenous glucose infusion will be averaged during the last 60 minutes to provide a quantitative measure of insulin-mediated primarily muscle total glucose disposal. Insulin infusion will be stopped and the study will be terminated at t 180 minutes. Patients will be observed for an additional 90 minutes after consuming a meal and they will be allowed to leave after plasma glucose is stable. 