An intestinal hormone called Glucose-dependent Insulinotropic Polypeptide (GIP) is released into the blood immediately after ingestion of a meal and plays an important role in regulating blood sugar levels. However, GIP is not active in persons with type 2 diabetes mellitus (T2DM) which is also known as adult onset or non-insulin-dependent diabetes. This study is being conducted to determine whether a hormone called xenin-25 can restore the activity of GIP in persons with T2DM.

Each eligible participant will be administered an oral glucose tolerance test so he/she can be assigned to the group with "normal glucose tolerance", "impaired glucose tolerance" (between normal and diabetic), or type 2 diabetes mellitus. Each study subject will then be administered a graded glucose infusion (GGI) on 4 separate occasions. For the GGI, an intravenous glucose infusion will be started at a rate of 1 mg x kg-1 x min-1 for 40 min, followed by 2, 3, 4, 6, and 8 mg x kg-1 x min-1 (40 min for each step). A primed-continuous infusion of vehicle alone, GIP alone, xenin-25 alone, or the combination of GIP plus xenin-25 (each peptide at a dose of 4 pmoles x kg-1 x min-1) will be initiated at the same time the glucose infusion is started. Blood samples will be collected before and during the GGI for the measurement of glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels.

Inclusion Criteria:

• Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
• Healthy volunteers with no clinical evidence of T2DM.
• Otherwise healthy volunteers that have impaired glucose tolerance.
• Otherwise healthy volunteers with diet controlled T2DM.
• Otherwise healthy volunteers with T2DM that take oral agents only if the subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48-hours.
• Persons with HbA1c less than 9%.
• Women of childbearing potential must be currently taking/using an acceptable method of birth control. A pregnancy test will be done at the beginning of each visit. Any woman with a positive pregnancy test will be removed from the study.
• Willingness to complete all required visits.

Exclusion Criteria:

• Lacks cognitive ability to sign the consent or follow the study directions.
• Women unwilling to use an acceptable method of contraception during the course of the study, or who are currently breast-feeding.
• Any subject whose screening HbA1c is >9.0%.
• Type 2 diabetes requiring the use of supplemental insulin at home.
• Volunteers with a history of Acute Pancreatitis.
• Volunteers with a history of cancer (except for skin cancer).
• Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides >400mg/ml) hypercalcemia (blood calcium level >11.md/dl) and/or the presence of gallstones.
• Volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass, documented gastro-paresis in diabetic volunteers.
• Subjects taking medications known to affect glucose tolerance.
• Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with the HemoCue 201+ is <11.2% mg/dlL).
• Diabetics that have the potential to have a low blood sugar without them being aware that their blood sugar is low (hypoglycemia unawareness).
• Significant systemic illness including heart, kidney, inflammatory, liver, or malignant disease requiring medications.
• Subjects will be excluded if their liver or kidney function is outside the upper limits of normal by > 3%. Total Bilirubin levels should be <2.
• Subjects unwilling to allow the use of human albumin in the preparation of the peptides.
• Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin