Modeling glucose disposal in diabetic dogs fed mixed meals

We have utilized a previously described mathematical model to study glucose disposal in fed, conscious, ambulatory, diabetic dogs. The model was applied to estimate the daily disposition of ingested glucose in the periphery, liver, and urine following a regular mixed meal containing 130 g of carbohydrate. Experimental data was obtained from 11 pancreatectomized animals. Both the portal and peripheral routes were used for intravenous insulin infusion and the daily profiles of peripheral plasma glucose and insulin concentrations measured. Total calories in mixed meals were derived from carbohydrates (37%), fat (30%), and protein (30%). When judged according to the root-mean-square differences, agreement was excellent between model-predicted and experimentally observed glucose as well as insulin concentrations. This agreement occurred whether or not, in addition to basal insulin, meal insulin was also given. Using the model, we then predicted in detail the rates of glucose uptake in peripheral tissue, liver, and kidneys. With portally infused insulin resulting in diurnal glycemic normalization, the net daily hepatic glucose balance was physiological, being close to zero. Remarkably, with peripheral insulin infusions there was an unphysiological net negative hepatic glucose balance of 10 g/day.