Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs

Aims/hypothesis: In non-diabetic people, insulin levels in the liver are two-fold higher than those in the systemic circulation. In contrast, patients with type 1 diabetes have similar hepatic and systemic insulin levels because insulin is administered peripherally. The aim of this study was to compare the effects of systemic (SI) and preportal (PI) insulin administration on energy, glucose and protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs. Materials and methods: We applied glucose-controlled insulin infusion, indirect calorimetry and stable isotope and radioisotope techniques to measure energy, protein and glucose metabolism. We maintained near-normoglycaemia at identical levels under both study conditions for 20 h. Results: SI was associated with lower oxygen consumption (130±13 vs 161±8 ml/min), CO₂ production (99±10 vs 130±8 ml/min), respiratory quotient (0.76±0.02 vs 0.81±0.01) and energy expenditure (870±90 vs 1089±60 kcal/24 h) (p<0.05 for all differences). PI increased the respiratory quotient from the insulin-deprived state, whereas SI did not. Glucose kinetics were similar for SI and PI, whereas leucine oxidation (36±4 vs 54±5 μmol kg^-1 min ^-1) and the fractional synthesis rates of liver tissue protein (0.68±0.6 vs 0.83±0.07%/h), albumin (0.55±0.06 vs 0.68±0.4%/h), and fibrinogen (1.73±0.23 vs 2.59± 0.25%/h) were all lower during SI than PI (p<0.05). Conclusions/interpretation: The route of insulin administration did not alter glucose metabolism but did affect protein synthesis in the liver. The potential impact of this altered liver protein metabolism on chronic complications needs careful evaluation. A similar decrease in energy expenditure resulting from systemic insulin administration during tight glycaemic control is a potential cause of weight gain.