To Define the Role of GLP-1 for Improving Glucose Homeostasis in Humans Following Gastric Bypass Surgery

To conduct this study, we will enroll humans who previously underwent Roux-en-Y gastric
bypass surgery, who are medically and weight stable and with no signs of type 2 diabetes
either before or after surgery. Potential subjects will first be screened for eligibility and
also to verify that they can safely participate in the study. Each study subject will be
administered a meal tolerance test (MTT) on 3 separate occasions. For the MTT, a liquid meal
(Boost Plus) will be ingested following an overnight fast. A primed-continuous infusion of
vehicle alone (human albumin) or xenin-25 alone (at a dose of 4 or 12 pmoles x kg-1 x min-1)
will be initiated 15 minutes before the meal is ingested. Blood samples will be collected
before and during the MTT for the measurement of glucose and insulin levels, as well as a
host of other hormones. A comparison of the results will tell us if the effects of xenin-25
on insulin release are mediated by GLP-1 in humans.

Inclusion Criteria:

- Individuals must be able to consent for their own participation (no mental impairment
affecting cognition or willingness to follow study instructions).

- Healthy, weight stable, with previous Roux-en-Y gastric bypass surgery and no clinical
evidence of type 2 diabetes either before and after Roux-en-Y gastric bypass surgery.

- Women of childbearing potential must be currently taking/using a method of birth
control that is acceptable to the investigators. 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 return have 8-10ml of blood drawn 25-30 days after the last Xenin
infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be
made to complete this visit during study participation.)

Exclusion Criteria:

- Lacks cognitive ability to sign the consent &/or follow the study directions for
themselves.

- Women unwilling to comply with using an acceptable method of contraception during the
course of the study, or who are currently breast-feeding.

- 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.

- 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 g/dl).

- Any major medical conditions, or conditions that in the opinion of the PI make the
subject unsuitable for the study.

- Subjects with abnormal kidney function as measured by the Creatinine concentration
will be excluded.

- Subjects with a history of active liver disease or AST/ALT levels >2X upper limit of
normal will also be excluded.

- Total Bilirubin levels should be <2.

- Subjects unwilling to allow the use of their own blood or albumin in the preparation
of the peptides. (The blood will prevent sticking of the peptide to the tubing; an
alternative method has been sought but not found.)

- Unwillingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin
infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be
made to complete this visit during study participation.)