Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs
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Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs. / Gradel, Anna Katrina Jógvansdóttir; Kildegaard, Jonas; Porsgaard, Trine; Lykkesfeldt, Jens; Refsgaard, Hanne Hoffman Frølund.
In: Basic & Clinical Pharmacology & Toxicology, Vol. 128, No. 6, 2021, p. 783-794.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs
AU - Gradel, Anna Katrina Jógvansdóttir
AU - Kildegaard, Jonas
AU - Porsgaard, Trine
AU - Lykkesfeldt, Jens
AU - Refsgaard, Hanne Hoffman Frølund
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1111/bcpt.13574
DO - 10.1111/bcpt.13574
M3 - Journal article
C2 - 33626236
VL - 128
SP - 783
EP - 794
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
SN - 1742-7835
IS - 6
ER -
ID: 257430810