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

Abstract

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.

Pattern of Postprandial Carbohydrate Metabolism and Effects of Portal and Peripheral Insulin Delivery

“…However, in our studies, the route of insulin delivery had no detectable effect on plasma lipids. These results are similar to those previously reported by Kruszynska et al (67) in rats and Goriya et al (68) in dogs. Of interest in our experiments, the plasma lactate concentrations tended to be higher in the portal group than the peripheral or sham-operated group.…”

“…Of interest in our experiments, the plasma lactate concentrations tended to be higher in the portal group than the peripheral or sham-operated group. In contrast, Goriya et al (68) observed increased lactate concentrations when insulin was infused into either the portal or the peripheral venous system. However, it should be noted that the 7-h square wave employed by Goriya et al resulted in systemic hyperinsulinemia regardless of whether insulin was infused into the portal or peripheral venous system.…”

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

“…Evidence as to relative efficiency of portal and peripheral delivery of insulin in the regulation of both glucose and other aspects of metabolism is not entirely consistent. Some studies have shown a relative superiority of portal infusion in the maintenance ofnormal metabolic parameters (5,6), including glycemia (6) and insulinemia (5). Other work indicates that the two routes of insulin entry are essentially equivalent (7)(8)(9).…”

“…The intraperitoneal route has been suggested since a porto-systemic gradient of insulin concentrations is generated that is similar to that seen physiologically ( 12,13). The therapeutic relevance of this gradient, however, is not yet resolved (5)(6)(7)(8)(9)(10)(11)14). A decrease in hepatic insulin uptake and therefore in the porto-systemic gradient is seen in liver disease (15)(16)(17) and is associated with insulin resistance suggestive ofa potential causative role for this hepatic lesion.…”

Combined subtotal pancreatectomy with selective streptozotocin infusion — a model for the induction of insulin deficiency in dogs

“…Intermittent suppression of insulin release is not practicable for long-term experiments [5,21]. Total pancreatectomy is subject to serious complications and disadvantages, such as alterations in food resorption and abdominal topography [3, 9,11], which restrict its application for many experiments. Beta-cell destruction is possible with alloxan and/or streptozotocin.…”