THE ROLE OF GLUCAGON IN REGULATING GLUCOSE PRODUCTION IN THE PROLONGED FASTED DOG (GLUCOSEOGENESIS, NON ESTERIFIED FREE FATTY ACIDS, AMINO ACIDS

The seven day fasted dog was used to assess the role of glucagon in regulating hepatic glucose production (R(,a)) when glycogen is depleted and gluconeogenesis provides the blood glucose. To regulate the level of glucagon, somatostatin was infused with intraportal replacement of insulin and glucagon. Four infusion protocols were followed: (1) Saline; (2) Hormone replacement (Control); (3) Glucagon deficiency; or (4) Glucagon excess.;All parameters were constant during saline infusion; insulin levels were stable in all protocols. The glucagon level was stable in controls, but was completely suppressed during glucagon deficiency and rose twenty fold during glucagon excess. The glucose level was constant at 99 (+OR-) 3 mg/dl and R(,a) was constant at 1.9 (+OR-) 0.1 mg/kg-min in controls. During glucagon deficiency the glucose level was held constant at 97 (+OR-) 3 mg/dl by glucose infusion but R(,a) had fallen 44% by 30 min. With glucagon excess the glucose level rose 103% by 45 min and R(,a) rose 273% by 15 min and then remained constant at a two fold basal rate. With saline the fractional extraction of alanine by the liver (AFE) was constant, during glucagon deficiency it fell by half and during glucagon excess it doubled. The efficiency of the gluconeogenic process was not significantly different in the saline, controls and glucagon excess protocols but during glucagon deficiency it was significantly reduced. Therefore, despite a prolonged fast glucagon regulates R(,a) principally by regulating flux through the glucagon mass. Basal glucagon levels are also responsible for maintaining the basal efficiency of AFE and the basal rate of gluconeogenesis.;In seven day fasted dogs, unlike 18h-fasted dogs, during controls the rate of glucose utilization (R(,d)) rose from 45%, alanine and lactate levels rose (90% and 238% resp.) and the FFA level fell from 54%. To assess if the fall in FFA stimulated R(,d), controls were infused with intralipid plus heparin. The FFA level was held constant at the basal level for 90 min and then doubled for the last 90 min. Insulin, glucagon and glucose levels were constant. During intralipid infusion the rise in R(,d) (22%) and alanine and lactate level (23% and 60%, in each case) were markedly blunted. This suggests that somatostatin suppresses plasma FFA levels which subsequently results in enhanced glucose utilization.