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?

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