title: Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: J
authors: J
authors: Fernandes
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: J
authors: J
authors: Vogt
authors: 1] Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada [2] Clinical Nutrition and Risk Factor Modification Centre and Division of Endocrinology and Metabolism and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
authors: T M S
authors: TM
authors: Wolever
mesh_terms: D000085:Acetates / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D000328:Adult; D003106:Colon / Q000378:metabolism*; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism*; D008297:Male; D012016:Reference Values
chemical_list: D000085:Acetates; D007328:Insulin