Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon Like Peptide 2

Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon Like

1. To assess whether Glucagon like peptide 2 (GLP-2) affects lipoprotein production (study A)
2. To assess whether GLP-2 affects the release of preformed chylomicrons (study B)

Study A: Using constant feeding with a nasoduodenal tube and stable isotope infusion, mathematical modelling will be utilised to measure lipoprotein production and clearance. The lipoproteins assessed will be apoB-100 from the liver and apoB-48 from the intestine.

StudyB: Volunteers will be given a liquid meal with retinyl palmitate (vitamin A) to label chylomicrons made from the meal. 7 hours later they will be given GLP-2 or placebo. Measurements of plasma and TRL(triglyceride rich lipoprotein) triglyceride and TRL retinyl palmitate will be carried out to see whether GLP-2 increases these parameters.

Inclusion Criteria:

• Inclusion Criteria:

  1. Men and women, aged 18 to 60 years
  2. Body mass index 20 kg/m2 to 30 kg/m2
  3. Hemoglobin above 130g/L.
  4. Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test (OGTT)

Exclusion Criteria:

• 1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.

  2. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180) or proliferative retinopathy 3. History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.

  4. Any history of ischemic heart disease or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.

  5. Abnormal liver or thyroid function tests 6. Current addiction to alcohol or substances of abuse as determined by the investigator.

  7. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 8. Taking any prescription or non-prescription medications at the time of the study 9. Having donated blood three months prior to and three months post study procedures 10. A pregnancy test will be performed 1 to 3 days prior to each study in all female research participants. Those who test positive for pregnancy will be excluded.