Fat Metabolism

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.