This study will look at two FDA approved medications that improve how the pancreas works in patients with Type 2 Diabetes. In order to understand how these medications work in patients with diabetes we must first measure the normal response in healthy volunteers without diabetes. We will be looking at the body's normal physiological response to low blood sugar and whether this will be modified by these medicationsThe hypothesis would be that glimepiride induced insulin secretion will be inhibited by hypoglycemia.

In patients with type 2 diabetes, sulfonylurea drugs are a mainstay for effective glucose control. These agents produce their hypoglycemic effects via stimulation of endogenous insulin secretion. Oversecretion of insulin, per se, or a continued relative increase of the hormone even when plasma glucose is normal will result in hypoglycemia. This latter situation commonly occurs if a patient decides to omit, delay, or reduce the size of a meal. An important defense against hypoglycemia in the above situations is glucose dependent regulation of insulin secretion. In other words, a low ambient glucose concentration could regulate the magnitude of the amount of insulin released in response to a sulfonylurea. Thus during hypoglycemic conditions, the sulfonylurea would result in little or no insulin secretion, whereas its effects during hyperglycemia would be amplified. Glimepiride and glyburide are both second-generation sulfonlyurea drugs used commonly for treatment of type 2 diabetes. This study will compare the two and ask the following question:

Is Glimepiride insulin secretion dependent upon glucose concentration in-vivo?

• Drug: Glimepiride
  Glimepiride (Amaryl) 4 mg oral dose during protocol, given once during each protocol.
  Other Name: Amaryl
• Drug: glyburide
  Glyburide (Dia-Beta) 10 mg oral dose during protocol, given once during each protocol.
  Other Name: Dia-Beta
• Other: glucose clamp
  Hyperinsulinemic euglycemic glucose clamp procedure-120 minutes
• Other: glucose clamp
  hypoglycemic glucose clamp procedure -120 minutes

• 1: Experimental
  Intervention: Drug: Glimepiride
• 2: Experimental
  Intervention: Drug: glyburide
• 3: Experimental
  control-euglycemia
  Intervention: Other: glucose clamp
• 4: Experimental
  control-hypoglycemia
  Intervention: Other: glucose clamp

Inclusion Criteria:

• Healthy male and female subjects aged 30-60
• Body Mass Index 21-30 kg/m2
• All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities
• EKG treadmill stress test for volunteers over 40 years of age.
• Female volunteers of childbearing potential will undergo HCG pregnancy test.

Exclusion Criteria:

• Prior or current history of poor health
• Abnormal results following screening tests
• Pregnancy
• History of allergy to sulfonylurea or related drugs