Insulin Infusion Into the Portal and Peripheral Circulations of Unanaesthetized Dogs

Abstract

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.

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

“…When meal insulin was infused initially, the animals receiving portal insulin had lower NEFA levels but toward the end of the meal infusion similar NEFA levels were observed indicating that maximum inhibition of lipolysis was present in both groups. Similar effects on NEFA in insulin infused dogs have been reported by others [13]. The comparison between the metabolic profiles in these two groups of diabetic animals brings out certain other significant differences.…”

“…Since the portal (natural) route is not readily accessible for experimental insulin replacement in man, a series of animal experiments in pancreatectomised dogs was conducted to evaluate this route of insulin replacement as compared with peripheral IV insulin administration. The effects of short term insulin infusions into the portal and peripheral circulations of unanaesthetised normal dogs have been reported [13].…”

Comparison of Superior Mesenteric Versus Jugular Venous Infusions of Insulin in Streptozotocin-Diabetic Rats on the Choice of Caloric Intake, Body Weight, and Fat Stores

“…Several studies have shown that portal venous infusion of insulin can result in reduced circulating insulin levels, compared with peripheral venous infusion (24), probably associated with greater liver insulin extraction (25). It therefore stands that an insulin-induced, liver-mediated signal may have resulted in the restoration of lard intake to nondiabetic levels.…”

Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs

“…h before and '/4, xh, %, 1, VA, l'A, l3A, 2, 2!4, 3, 4, 5 and 6 h after terminating the infusion for measurement of calcium and phosphate as previously described (Stevenson et al 1978). Plasma 47Ca was meas¬ ured in a Packard Gamma Spectrometer and corrected for background.…”

“…A fresh minipump was implanted sc in the dog's back every 7 days and the infusion rate adjusted to produce plasma calcium increases of 0.4 to 0.7 mmol/I. After 4 weeks, each dog was prepared with two indwelling cannulae in the superior vena cava, the infusion cannula being 3 cm nearer the atrium than the cannula for blood sampling, as previously described (Stevenson et al 1978). The sc infusion was then replaced by an iv infusion of hPTH 1-34 at a rate designed to produce a similar plasma calcium increase.…”