Abstract
Two classes of inositol phosphoglycans have been implicated as second messengers of insulin, one that activates pyruvate dehydrogenase and contains D-chiroinositol, and one that inhibits cyclic AMP–dependent protein kinase and contains myoinositol. We examined the effects of a 3-day fast on muscle contents of inositols in healthy humans. An oral glucose tolerance test was performed and a biopsy was obtained from the quadriceps femoris muscle after an overnight fast and after a 72-hour fast. The 72-hour fast significantly increased plasma glucose (1.5- to 2-fold) and insulin (2- to 4-fold) after glucose ingestion versus the values after the overnight fast, indicating the manifestation of peripheral insulin resistance. The 72-hour fast resulted in an ∼20% decrease in the muscle content of D-chiroinositol (P < 0.02), but no change in the myoinositol content. These data demonstrate that fasting specifically decreases the muscle content of D-chiroinositol in human muscle and this may contribute to the finding that insulin-mediated activation of pyruvate dehydrogenase is attenuated after short-term starvation.
Highlights
Larner and coworkers first proposed the existence of a putative mediator of insulin action [1]
In the Rhesus monkey, a linear relationship between the 24-hour urinary chiroinositol excretion rate and insulin resistance was demonstrated by 5 independent methods, including glucose disposal rates during euglycemic hyperinsulinemia, serum glucose disappearance rates after intravenous glucose injection, and muscle and fat biopsy determinations of glycogen synthase and phosphorylase activity states [21]
Japanese subjects with normal glucose tolerance, impaired glucose tolerance, and type II diabetes were compared with regard to 24-hour urinary chiroinositol excretion and insulin sensitivity
Summary
Larner and coworkers first proposed the existence of a putative mediator of insulin action [1]. Short-term starvation is associated with insulin resistance in humans. Short-term starvation results in decreased basal and insulin-mediated muscle glucose uptake and carbohydrate oxidation [13,14,15], which may be a consequence of diminished D-chiroinositol availability. The purpose of the present study, was to determine the effects of a 3-day fast on the muscle contents of inositols in healthy humans
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