Effect of Physiologic Hyperglucogonemia on Adipocyte Metabolism

HSC20170682H

Purpose/Objectives: To investigate the effect of hyperglucagonemia on insulin action, particularly on adipose tissue. Research Design/Plan: Normal glucose tolerant subjects will be studied. Study subjects will receive a continuous glucagon infusion for 12 hours. Following glucagon infusion, subjects will receive prime-continuous tracer infusions for additional 4 hours to measure adipocyte metabolism. Within 6-8 weeks, subjects will return for a repeat study with normal saline as a control group. Methods: All subjects will have an oral glucose tolerance test prior to participation to confirm they are normal glucose tolerant. Subjects will be admitted to the CRC at 4 PM and will receive a continuous glucagon for 12 hours. At 6 AM on the following morning, subjects will receive prime-continuous tracer infusions of the following for 4 hours (14C-glycerol, 3-3H glucose, and D2O). At 10 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes. At 6 AM a surgical biopsy of abdominal adipose tissue will be performed for measurement of adipocyte metabolism. At 8 AM, the study team will infuse insulin/glucose to test for insulin sensitivity. Clinical Relevance: The results of this study will help the study team to further understand the pathophysiology of metabolic disturbances that is induced by hyperglucagonemia in type 2 diabetes patients.

2018-02-05

2025-12-30

2026-08-25

Active (not recruiting)

Early phase I

10

Inclusion Criteria: 1. Fasting Glucose \< 100 mg/dl 2. HbA1C \< 5.7% 3. 2-h OGTT value \< 140 mg/dl 4. Good general Health as determined by medical history, physical exam, screening lab tests, urinalysis, and EKG. 5. Weight Stable (±3 lbs) over the preceding 3 months 6. ages from 18-50 7. Male/Female 8. BMI from 23-28 kg/m2 - Exclusion Criteria: 1. Subjects who participate in an excessively heavy exercise program. 2. Subjects taking any medication known to affect glucose tolerance will be excluded. 3. Cannot be pregnant 4. Hyper sensitive to glucagon -

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2023-09-26