MENHADEN OIL PREVENTS BUT DOES NOT REVERSE SUCROSE-INDUCED INSULIN-RESISTANCE IN RATS

Although fish oil supplementation may prevent the onset of diet-induce d insulin resistance in rats, it appears to worsen glycemic control in humans with existing insulin resistance. In the present study, the eu glycemic, hyperinsulinemic (4X basal) clamp technique with [3-H-3]gluc ose and 2-deoxy-[1-C-14]glucose was used to directly compare the abili ty of fish oil to prevent and reverse sucrose-induced insulin resistan ce. In study 1 (prevention study), male Wistar rats were fed a purifie d high-starch diet (68% of total energy), high-sucrose diet (68% of to tal energy), or high-sucrose diet in which 6% of the fat content was r eplaced by menhaden oil for 5 wk. In study 2 (reversal study), animals were fed the high-starch or high-sucrose diets for 5 wk and then the sucrose animals were assigned to one of the following groups for an ad ditional 5 wk: high starch, high sucrose, or high sucrose with 6% menh aden oil. Rats fed the high-starch diet for 10 wk served as controls. In study 3 (2nd reversal study), animals followed a similar diet proto col as in study 2; however, the reversal period was extended to 15 wk. In study 1, the presence of the fish oil in the high-sucrose diet pre vented the development of insulin resistance. Glucose infusion rates ( GIR, mg kg(-1) min(-1)) were 17.0 +/- 0.9 in starch, 10.6 +/- 1.7 in s ucrose, and 15.1 +/- 1.5 in sucrose with fish oil animals. However, in study 2, this same diet was unable to reverse sucrose-induced insulin resistance (GIR, 16.7 +/- 1.4 in starch, 7.1 +/- 1.5 in sucrose, and 4.8 +/- 0.9 in sucrose with fish oil animals). Sucrose-induced insulin resistance was reversed in rats that were switched back to the starch diet (GIR, 18.6 +/- 3.0). Results from study 3 were similar to those observed in study 2. In summary, fish oil was effective in preventing diet-induced insulin resistance but not able to reverse it. A preexist ing insulin-resistant environment interferes with the positive effects of menhaden oil on insulin action.