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Carbohydrates, glycemic index and diabetes mellitus

Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans

Abstract

Background/objectives:

The short chain fatty acid acetate (AC), may have 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 (NI) and hyperinsulinaemic (HI) participants. Therefore, we studied AC absorption from the distal colon in participants with normal (<40 pmol/l) and high (40 pmol/l) plasma insulin. This work was a part of a series of studies conceived to compute a kinetic model for AC. 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 AC (90 mmol/l). The solutions were retained for 40 min, then voided for AC measurement. Total amount of AC infused was 27 mmols.

Results:

AC 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.

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Abbreviations

(List of abbreviations used in the calculation of acetate (AC) kinetics): A:

rate of AC absorption from the distal colon

[AC]FO:

fasting [AC] on the oral glucose tolerance test (OGTT) test day

[AC]FR:

fasting [AC] on the rectal infusion day

[AC]NO:

nadir of serum AC after 75g oral glucose

C :

AC clearance

H :

rate of hepatic uptake of AC

P end :

amount of endogenous AC produced from fat metabolism

P exog :

amount of exogenous AC produced from colonic fermentation

X :

rate of entry of AC into peripheral blood

X end :

rate of endogenous AC production from fat metabolism

X exog :

rate of exogenous AC production from colonic fermentation

X f :

sum of the rate of endogenous and exogenous AC production at fasting (Xend + Xexog)

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Acknowledgements

This study was supported by grant no. OOP-64648 from the Canadian Institutes for Health Research (CIHR), Institute of Nutrition, Metabolism and Diabetes.

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Correspondence to T M S Wolever.

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Fernandes, J., Vogt, J. & Wolever, T. Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans. Eur J Clin Nutr 68, 1067–1071 (2014). https://doi.org/10.1038/ejcn.2014.136

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