The aim of the present study was to determine the role of insulin and glucagon in the regulation of basal gluconeogenesis in overnight-fasted anesthetized dogs. A deficiency of either or both pancreatic hormones was achieved by infusing somatostatin (1 μg./kg./min.), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72±6 per cent and 81±8 per cent, respectively. Intraportal infusions of insulin and glucagon at rates of 400 μU./kg./min. and 1 ng./kg./min., respectively, resulted in the maintenance of the basal levels of each hormone. Gluconeogenesis was assessed by measuring both the splanchnic extraction of alanine and the conversion of 141C-alanine into l4C-glucose.

Isolated glucagon deficiency (basal insulin level maintained) resulted in a 44±9 per cent (P <0.05) decrease in the conversion rate of alanine into glucose. Isolated insulin deficiency (basal glucagon level maintained) resulted in a 74±7 per cent (P <0.01) increase in the conversion rate of alanine into glucose. Somatostatin had no effect on alanine conversion into glucose when the changes in the pancreatic hormone levels that it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon. A deficiency of either hormone for up to 60 minutes failed to alter the splanchnic extraction rate of alanine.

In conclusion, in the overnight-fasted anesthetized dog, (1) basal glucagon plays a significant role in the stimulation of gluconeogenesis from alanine, (2) basal insulin exerts a potent inhibitory effect on the rate of conversion of alanine into glucose, with the result that glucagon's gluconeogenic potential is markedly enhanced during insulin deficiency, and (3) somatostatin has no acute effects on gluconeogenesis from alanine other than those it induces through perturbation of pancreatic hormone secretion. This study indicates that the opposing actions of the two pancreatic hormones are important for the fine regulation of gluconeogenesis.

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