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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GLP=2 | Experimental | active treatment with a single dose of GLP-2 (1500mcg) |
|
| Placebo | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-2 | Drug | single subcutaneous dose of 1500mcg |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Lipoprotein production and clearance rate | ApoB 100 and ApoB 48 production and clearance | 10 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma and TRL triglyceride and TRL retinyl palmitate | Measurements will be carried out hourly after ingestion of meal and then every 15-30 minutes thereafter to see if GLP-2 increases these parameters compared to placebo. | 10 hours |
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Inclusion Criteria:
Inclusion Criteria:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toronto General Hospital | Toronto | Ontario | M5G 1L7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25173752 | Derived | Dash S, Xiao C, Morgantini C, Connelly PW, Patterson BW, Lewis GF. Glucagon-like peptide-2 regulates release of chylomicrons from the intestine. Gastroenterology. 2014 Dec;147(6):1275-1284.e4. doi: 10.1053/j.gastro.2014.08.037. Epub 2014 Aug 28. |
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| ID | Term |
|---|---|
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D053767 | Glucagon-Like Peptide 2 |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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| Placebo | Drug |
|
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |