An important but unanswered question remains concerning the role of glucagon in fasting. The fasting state is characterized by glycogen depletion and acceleration of gluconeogenesis from amino acids. Glucagon has been shown to be a potent stimulator of gluconeogenesis yet the role of glucagon in accelerating or maintaining gluconeogenesis in fasting is only partially understood. I propose to investigate the role of gluconeogenesis in fasting by performing hepatic vein-brachial arterty catheterization studies in 48-h fasted men. 14C-alanine will be administered by constant infusion and its conversion across the splanchnic bed to 14C-glucose will be followed as an index of gluconeogenesis. In addition somatostatin will be infused to inihibit endogenous insulin and glucagon secretion to allow investigator control of circulating pancreatic hormone levels. Four protocols will be performed. In the first, somatostatin will be infused to produce combined insulin and glucagon deficiency with euglycemia being maintained via exogenous glucose infusion. Protocols II & III will be similar to Protocol I except that an infusion of insulin and glucagon will be administered in Protocols II & III respectively to maintain either insulin or glucagon at its basal concentration. In Protocol IV both insulin and glucagon will be replaced in basal amounts. Thus, in Protocol II, the effects on gluconeogenesis of isolated glucagon deficiency will be examined and in Protocol III, the effects of isolated insulin deficiency. In Protocol IV, any effects of somatostatin itself will be monitored by replacing both hormones during somatostatin administration. These protocols will allow us to assess the role of glucagon in maintaining gluconeogenesis in fasting by selectively removing glucagon and by selectively removing insulin with glucagon maintained.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000095-25
Application #
3089765
Study Section
General Clinical Research Centers Committee (CLR)
Project Start
1977-12-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
25
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
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