Effect of interaction between insulin and glucagon on glucose turnover and FFA concentration in normal and depancreatized dogs

We showed previously that arginine increased glucose production (R_a) and utilization (R_d) synchronously in normal dogs and suggested that this was due to concurrent insulin and glucagon release. In order to investigate the metabolic effects of coincidently elevated insulin and glucagon levels on R_a and R_d, glucagon was infused (1.55 μg/kg/hr) into normal dogs and into depancreatized dogs coincident with graded amounts of insulin (250–3000 μU/kg/min) until the metabolic response of the normal dog was achieved in depancreatized dogs. Main observations: Concurrent insulin and glucagon elevations increased glucose turnover (100%) in normal and depancreatized dogs while maintaining normoglycemia. Glucagon had no appreciable effect on peripheral glucose clearance in depancreatized dogs maintained on basal insulin. The effect of glucagon on R_a was not inhibited by concurrent insulin infusion at rates up to 3000 μU/kg/min. The effect of glucagon on R_a waned with time, indicating that a given insulin/glucagon ratio did not have a sustained effect. Near normal metabolic effects with respect to glucose turnover and FFA concentration were achieved in depancreatized dogs when the normal IRI response to glucagon was reproduced, indicating that the spike pattern of insulin release reflects not only the inherent secretory characteristic of β cells, but also serves an important glucoregulatory function. Glucagon induced an increase in ¹⁴C-glucose recycling, suggesting that it enhanced gluconeogenesis.