INSULIN INFUSION INTO THE PORTAL AND PERIPHERAL CIRCULATIONS OF UNANAESTHETIZED DOGS

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Abstract
Changes in glucose, phosphate, K, non-esterified fatty acids (NEFA) and insulin in peripheral venous blood were compared in 5 unrestrained fasted dogs during different rates of insulin infusion by the portal and peripheral circulation. The low rate of insulin infusion that was required to produce a fall in plasma glucose of 0.56-0.83 mmol/l (0.024 u[units]/kg per h female, 0.012 u/kg per h male). Two- and 4-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 hypoglycemia when given peripherally than intraportally. 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 hypoglycemia accompanied this fall during portal infusion suggests that these low doses of insulin had a direct effect on glucose metabolism in the liver. This hepatic action appears to be overwhelmed by peripheral uptake of glucose at the high rates of insulin infusion. A qualitatively different 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.