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Comparison Of The Metabolic Responses To Portal And Peripheral Infusions Of Insulin In Diabetic Dogs.

R. W. Stevenson, J. Parsons, K. Alberti
Published 1981 · Medicine

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Abstract The changes in peripheral blood levels of insulin and glucagon and in multiple indices of carbohydrate metabolism were compared in seven dogs, made diabetic with alloxan and streptozotocin, during insulin infusion by the portal and peripheral circulations. Each experiment was carried out in unrestrained fasted dogs after insulin had been withheld for 24 hr. Increasing the rate of insulin infusion from 0.006 to 0.05 U kg −1 h −1 for 2.5 hr caused a significantly greater reduction of peripheral blood glucose only at the infusion rate of 0.05 U kg −1 h −1 when the hormone was given peripherally than intraportally. Plasma levels of lactate, alanine and glycerol rose during the 2.5 hr control infusions of the vehicle while there was no change in the levels of 3-hydroxybutyrate. Peripheral infusion of insulin reduced the levels of glycerol and 3-hydroxybutyrate at all infusion rates but lactate and alanine levels were only reduced when the infusion rate was increased to 0.025 U kg −1 h −1 , a rate which produced measurable increases in peripheral plasma insulin. Portal infusions which did not elevate peripheral insulin levels caused a reduction in all four metabolites. The glucagon levels in the diabetic dogs were markedly decreased by insulin infusion of 0.012 U kg −1 h −1 by either route and the magnitude of this fall was similar at all higher infusion rates. Thus, the difference in responses to infusion of insulin by the portal and peripheral routes cannot be accounted for by the glucagon fall. We conclude that intraportal administration of insulin at rates of 0.006–0.05 U kg −1 h −1 reduces plasma levels of glucose and the metabolites studied by a direct action on the liver and would suggest that the hepatic action of peripherally administered insulin is manifest only when the infusion rate is increased to 0.025 U kg −1 h −1 .
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