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The metabolic and hormonal consequences of long term intravenous insulin replacement were studied in 11 pancreatectomised dogs. Insulin was delivered into the portal circulation of six animals for 164-224 days and into the peripheral circulation of the remainder for 123-365 days. Infusion rates were initially adjusted to achieve normoglycaemia in the fasting (0.37 +/- 0.01 mU Kg-1 min-1 portal; 0.45 +/- 0.03 mU kg-1 min-1 peripheral) and post-prandial states (2.57 +/- 0.07 mU kg-1 min-1 for 7 1/2 h portal; 3.16 +/- 0.18 mU kg-1 min-1 for 7 h peripheral). Animals were fed their usual mixed diet and blood samples were drawn from indwelling catheters at regular intervals for 24 h. A matched group of six normal dogs was similarly studied. Significantly less insulin was needed for glycaemic normalisation with portal (1.05 +/- 0.03 U kg-1 day-1) compared with peripheral (1.27 +/- 0.08 U kg-1 day-1) infusions, but post-prandial insulin levels were not normalised. Glucagon levels were normal and unaffected by the route of insulin infusion. Lactate and pyruvate responses were exaggerated post-prandially in the diabetic compared with the normal dogs. Fasting non-esterified fatty acid levels were suppressed with peripheral but normal with portal insulin infusion. There were only minor differences in the branched chain, essential and other non-essential amino acids except for alanine which was significantly above normal in the diabetic animals. Fasting levels of insulin, lactate, pyruvate and non-esterified fatty acids were normalised only with portal infusion while glucose, glucagon, 3-hydroxybutyrate and most amino acids were normalised regardless of the route of infusion. We conclude that the metabolic regulation achieved with portal insulin replacement is closer to normal than that achieved with peripheral infusion.

diabetologia

The metabolic and hormonal responses to a mixed meal in umestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion