Acute Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon

• Status: Completed
• Trial end date: 2010-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Insulin resistant states are characterized by hepatic lipoprotein (VLDL) particle overproduction. Numerous hormonal and nutritional factors are known to influence hepatic lipoprotein particle production, including insulin and free fatty acids (FFA). In contrast to the liver, the intestine has traditionally been viewed as a 'passive' organ with respect to lipoprotein production, with intestinal lipoprotein particle production determined mainly by the amount of fat ingested and absorbed. Glucagon plays a key role in the regulation of carbohydrate and fatty acid metabolism and has recently been shown for the first time to regulate hepatic lipoprotein production in mice. Ours will be the first study to investigate the effect of glucagon on hepatic and intestinal lipoprotein production in humans.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

1. Men and women, aged 18 to 40 years

2. Body mass index 20 kg/m2 to 25 kg/m2

3. Hemoglobin above 130g/L.

4. Normal glucose tolerance in response to a 75g, 2-hr 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. Fasting blood glucose > 6.0 mmol/l or known diabetes.

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

5. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l

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 subjects. Those who test positive for pregnancy will be excluded.