The response of peripheral tissues to
insulin is reduced in fasting and
diabetes mellitus. The experiments described herein were designed to determine whether
insulin-stimulated
glucose oxidation is affected by the
free-fatty acid-derived plasma metabolites
acetone,
acetol, and
propylene glycol (
1,2-propanediol [1,2-PD]), concentrations of which are elevated in both
starvation and
diabetic ketosis. In epididymal adipose tissue from fed and 48-h--fasted rats given 3%
acetone drinking water for 7 days,
insulin-stimulated
glucose oxidation was reduced by approximately 30-40%. After ingestion of 2%
acetol for 7 days, basal and
insulin-stimulated
glucose oxidation was lowered approximately 30%, whereas the consumption of 1,2-PD had no influence on either basal or
insulin-stimulated
glucose oxidation. Similar effects on
glucose oxidation were observed in isolated adipocytes from fed rats after ingestion of 3%
acetone and 2%
acetol for 7 days. The reduction in
insulin-stimulated
glucose oxidation in adipose tissue in vitro required the consumption of 3%
acetone water for greater than 3 days. In 48-h--fasted rats that ingested 3%
acetone for 5 days,
insulin-stimulated
glucose oxidation remained depressed 4 days after withdrawal of
acetone from the
drinking water. These studies imply that at least part of the
insulin resistance indigenous to fasting and
diabetic ketosis may be attributed to the metabolic influence of
acetone and/or
acetol in body fluids.(ABSTRACT TRUNCATED AT 250 WORDS)