Abstract
To clarify the significance of portal insulin delivery in glucose control, the effects of insulin infused via the peripheral (Pe) or portal (Po) route on glucose flux and glycemic response during i. v. glucose load (10 mg/kg/min for 60 min) were examined using artificial endocrine pancreas (AP) in five depancreatized dogs. The hepatic production rate (Ra) and metabolic clearance rate (MCR) of glucose were calculated by the tracer method. The extraction rate of glucose by unilateral hind limb (EX) determined by A-V difference technique was used as an index for peripheral glucose disposal. Data shown are means±SD of the last 30 min of glucose challenge.
Ra was suppressed more than 80% from prevalues in all experiments. The Po delivery route resulted in less Ex (10.3±2.0vs 15.7±3.4%) but the same glycemic response (171 ±22 vs 175 ± 19) and MCR (4.8±0.6 vs 4.3± 0.7ml/kg/min) in spite of lower peripheral IRI levels (13.2±5.8 vs 23.8±6.1 μU/ml) compared with the Pe route. Po insulin infusion (170%) augmented by AP achieved physiological peripheral IRI levels (20.8 μU/ml), but this increase in Po insulin dosage had no significant effects on either glycemia (166±20 mg/dl) or MCR (5.0±0.4ml/kg/min). These data suggest that the Po insulin delivery route results in a smaller gain in hepatic glucose handling and enhances splanchnic glucose uptake. Thus the Po access for insulin administration appears to be more suitable and safer for long-term clinical use in terms of stable glycemic control.
