Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs

Abstract

In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels-occurring as the result of glucose infusion or food intake-could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c-peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.

Keywords: Insulin absorption; insulin clearance; insulin pharmacokinetics; subcutaneous; variability.