Insulin infusion into the portal and peripheral circulations of unanaesthetized dogs.

Changes in glucose, phosphate, potassium, non-esterified fatty acids (NEFA) and insulin in peripheral venous blood were compared in five unrestrained fasted dogs during different rates of insulin infusion by the portal and peripheral circulation. The 'low' rate of insulin infusion was that required to produce a fall in plasma glucose of 0.56-0.83 mmol/l (0.024 u/kg/h female, 0.012 u/kg/h male). Two-fold and four-fold higher rates are referred to as 'medium' and 'high' rates, respectively. In all dogs, dose-related reductions in the glucose concentration of peripheral blood resulted from increasing the rate of insulin by either route. At 'low' and 'high' rates of infusion the net response was independent of the route of administration, but the 'medium' rate of insulin infusion led to a greater degree of hypoglycaemia when given peripherally than intraportally. As expected, insulin infused peripherally resulted in graded increases in peripheral insulin levels as the rate of infusion was increased from low to high while, paradoxically, intraportal administration at low and medium infusion rates resulted in a mean decrease of peripheral insulin levels from control, the low-dose producing the most consistent fall. The fact that hypoglycaemia accompanied this fall during portal infusion suggests that these low doses of insulin had a direct effect on plasma phosphate resulting from the change in route of administration of insulin (i.e. increase during portal and decrease during peripheral infusion) also suggests a direct hepatic effect of insulin given intraportally.