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

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.