The Effects Of Sea Cucumber Cerebroside On High Fructose Induced Insulin Resistance In Rats

In recent years, fructose consumption in diet increased dramatically.Consequently, the morbidity of the metabolic syndrome (MS) increased and thepatients with MS tended to be younger people. MS had become one of the mostdangerous factors to human health. The main pathogenesis of MS was insulinresistance which had become a focus of research worldwide. The model of rat insulinresistance induced by high fructose diet was used to research the pathogenesis ofinsulin resistance because it is close to the natural course of insulin resistance ofhuman beings. In addition, the sea cucumber cerebroside, a kind of the sphingolipid,is rich in Cucumaria frondosa. Few of reports focused on the effects of sea cucumbercerebroside on insulin resistance. This study compared and evaluated sea cucumbercerebroside and its main structure unit ceramide on the improvement of insulinresistance induced by high fructose in rats. Meanwhile, the mechanisms of glucoseand lipid metabolism were explored as well.First of all, it was successful to induce insulin resistance and hypertension in ratby70%fructose diet, characterized by impaired glucose tolerance, insulin sensitivitydeclining, hyperinsulinemia and hypertension. Sea cucumber cereboside and ceramidecould ameliorate hyperglycemia and hyperinsulinemia, and meanwhile decreased theblood pressure by releasing serum nitric oxide. Compared with ceramide, cerebosidehad better effects. The storages of blood glucose in body mainly include liverglycogen synthesis, muscle glycogen synthesis and lipid synthesis. Therefore, thestudy of mechanisms of sea cucumber cereboside and ceramide improving insulinresistance mainly concentrated on the glucose and lipid metabolism in liver, skeletalmuscle and adipose tissue.In terms of glucose metabolism, the effects of the sea cucumber cereboside andceramide on the tissues sensitive to insulin were discussed respectively. To investigatehow sea cucumber cereboside and ceramide improve insulin resistance induced byhigh fructose diet, we studied the glucose uptake and utilization, glycogen synthesisand degradation, gluconeogenesis, insulin signal transduction and inflammatory factors, respectively. All above were based on the changes of liver glycogen andmuscle glycogen. It was found that the sea cucumber cerebroside and ceramide playedpositive roles in improving glucose tolerance and insulin resistance. They alsoincreased the glucose intake in liver and skeletal muscle and promoted glycogensynthesis and insulin signal transduction in liver, inhibiting gluconeogenesis and theexpression of inflammatory cytokines in adipose tissue. But the mechanism ofceramide from sea cucumber improving insulin resistance was not identical tocerebroside. Ceramide could stimulate glucose uptake in adipose tissue, accelerate themuscle glycogen synthesis by promoting insulin signal transduction in skeletal muscle.However, ceramide could not inhibit gluconeogenesis in muscular tissue and couldnot promote the glucose uptake in liver and muscle, showing the opposite results ofcerebroside.Lipid metabolic disorder was one of the important reasons for insulin resistance.Next, we discussed the effects of sea cucumber cerebroside and ceramide oncholesterol metabolism in liver. Sea cucumber cerebroside and ceramide had nosignificant effects on serum TC and TG in rats. They could not improvehypercholesterolemia induced by high fructose as well. But they could decrease serumLDL-C and total liver cholesterol dramatically. By investigating the expression ofcholesterol metabolism related genes in liver, we found that sea cucumber cerebrosideand ceramide could increase the expression of LDL receptor, HMG reductase andSREBP2, and showed no effect on CYP7A mRNA expression. It was declared thatthey both promoted the liver cholesterol intake and endogenous synthesis and showedno effect on cholesterol oxidation decomposition. We speculated that cerebroside andceramide decreased cholesterol pool and improved liver cholesterol metabolism byinhibiting the reabsorption of cholesterol in enterohepatic circulation.The study found the effects of sea cucumber cerebroside and ceramide on insulinresistance induced by high fructose diet at the first time. The results could offer usefultheoretical basis for the utilization of cerebroside and the deep-processing of seacucumber.