Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans

BACKGROUND/OBJECTIVES: The short chain fatty acid acetate (AC), may play a role in increasing insulin sensitivity, thus lowering risk for obesity and type 2 diabetes mellitus. It is unclear if AC kinetics is similar in normal and hyperinsulinaemic participants. Therefore, we studied AC absorption from the distal colon in participants with normal (<40 pmol/L, NI) and high (≥40 pmol/L, HI) plasma-insulin. This work was part of a series of studies conceived to compute a kinetic model for acetate. Kinetic parameters such as estimates of rate of entry into peripheral blood, hepatic uptake and endogenous/exogenous production were compared in the groups. SUBJECTS/METHODS: Overnight fasted NI (n = 9) and HI (n = 8) participants were given rectal infusions containing sodium acetate (90 mmol/L). The solutions were retained for 40 min, then voided for AC measurement. Total amount of AC infused was 27 mmols. RESULTS: Acetate absorption from the distal colon (279±103 vs 322±91 μmol/min, P = 0.76) and hepatic uptake of AC (155±101 vs 146±85 μmol/min, P = 0.94) were similar in the groups. Endogenous and exogenous AC production was significantly higher in NI than HI participants. Plasma AC was inversely proportional to plasma insulin concentrations in the entire cohort (y=k/x, where k = 1813). CONCLUSIONS: There was low power to detect differences in AC absorption rate and hepatic AC uptake in NI vs HI. The rate of entry of AC into peripheral blood was similar in NI and HI participants. However, hyperinsulinaemia may alter endogenous and exogenous AC metabolism.