The purpose of this investigation was to determine the effects of
Phytostanol Phosphoryl Ascorbate (FM-VP4) on
insulin resistance,
hyperglycemia, plasma
lipid levels,
body weight, and gastrointestinal absorption of exogenous
cholesterol in Zucker (fa/fa) fatty and lean rats. A group of 12 age-matched male obese (n = 6) and lean (n = 6) Zucker rats were administered 250 mg/kg twice a day (
as 2% FM-VP4 in
drinking water) for 30 consecutive days. Fasted blood samples prior to and following treatment were taken from all rats for
glucose,
lipid,
insulin, and
leptin determination. An oral
glucose tolerance test was also carried out at the end of the treatment protocol. In addition, male obese (n = 7) and lean (n = 8) Zucker rats were coadministered a single oral gavage of [(3)H]
cholesterol plus cold
cholesterol with or without FM-VP4 (20 mg/kg) dissolved in
Intralipid and the plasma concentration of the radiolabel was determined 10 h following the dose. FM-VP4 30-day treatment did not alter
body weight, morning
glucose,
insulin,
lipids, and
leptin concentrations. There was no alteration in
glucose tolerance in the nondiabetic, normoglycemic lean group; however, there was a highly significant improvement in
glucose tolerance in the fatty group following FM-VP4 treatment. In addition, the
insulin response to oral
glucose showed no significant change in nondiabetic lean rats, whereas there was a change in the
insulin secretory profile in the fatty group following FM-VP4 treatment. Furthermore, following a single oral gavage of FM-VP4 resulted in a significant decrease in the percentage of radiolabeled
cholesterol absorbed. These findings suggest that FM-VP4 treatment to fatty Zucker rats could result in increased
glucose responsiveness of the
insulin secreting pancreatic beta cells. Furthermore, our findings suggest that FM-VP4 may only be effective presystemically. Systemic administration of FM-VP4 is warranted to determine the therapeutic potential of this effect.