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Aims/Introduction  Sphingosine‐1‐phosphate ( S 1 P ), a multifunctional bioactive lipid mediator, is involved in various diseases. Apolipoprotein  M  ( A po M ) carries  S 1 P  on high‐density lipoprotein and modulates  S 1 P  metabolism to increase the total  S 1 P  mass in the body. Both  S 1 P  and  A po M  are involved in diabetes.    Materials and Methods  The present study examined the modulation of  S 1 P  and  A po M  levels in the plasma, liver and kidneys in streptozotocin‐induced diabetes ( STZ ) mice, and the effects of insulin on the  S 1 P  and  A po M  levels in the plasma and liver in  STZ  mice and normal mice. We also examined the effects of insulin and glucose on the  A po M  levels in  H ep G 2 cells.    Results  In  STZ  mice, both the plasma  S 1 P  and  A po M  levels were higher than those in control mice. The hepatic  S 1 P  and  A po M  contents were also elevated. The hepatic  S 1 P  and  A po M  contents were reduced by insulin treatment, whereas high‐dose insulin decreased the plasma  S 1 P  and  A po M  levels. In mice without streptozotocin treatment, the administration of insulin decreased the plasma  S 1 P  and  A po M  levels, and the hepatic content of  A po M , whereas the hepatic level of  S 1 P  was not altered. Treatment with insulin and incubation under a low glucose level decreased the  A po M  levels in  H ep G 2 cells. Regarding the kidney, the renal levels of  S 1 P  and  A po M  were increased in  STZ  mice, and insulin treatment partially restored this increment.    Conclusions  In  STZ  mice, the levels of  S 1 P  and  A po M  in the plasma, liver, and kidneys were increased. Insulin treatment somehow reversed this modulation in  STZ  mice.

Modulation of sphingosine‐1‐phosphate and apolipoprotein M levels in the plasma, liver and kidneys in streptozotocin‐induced diabetic mice