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Background Objective: Diabetes has become one of the three diseases affect people's quality of life, health and even lives, its pathogenesis major defects of islet function and insulin resistance (Insulin resistance, IR) two factors, but the exact pathogenesis is still not clear. With further research, have been found the sphingomyelin (Sphingomyelin, SM), and its precursor ceramide has been the accumulation of the patient's body in the IR. SM is sphingomyelin synthase (Sphingomyelin synthase, SMS) catalytic lecithin phosphorylcholine transferred to the hydroxyl group of the ceramide generated; SMS SM de novo synthesis pathway critical synthase, there are two subtypes SMS1 and SMS2 ; wherein the SMS2 main synthase, is positioned in the cell membrane. In this study, sphingomyelin synthase 2 gene knockout (Sphingomyelin synthase 2 knockout, SMS2 - / - ) mice for research to explore the relationship of sphingomyelin synthase 2 diabetes development. The experimental method: select male, 3-month-old mice SMS2 - / - for the experimental group; male, 3-month-old C57BL/6J (wild-type, WT) mice were used as a control group. The high-calorie diet and two groups of mice before and after weight measured, fasting blood glucose (Fasting plasma glucose, FPG), fasting insulin (Fasting insulin, Fins) and impaired glucose tolerance. High calorie diet fed for three months after insulin release test (Insulin release test, IRT) and insulin tolerance test (Insulin tolerance test, ITT). Insulin resistance index, linear regression analysis. Eventually take epididymal adipose paraffin sections mice were sacrificed, and calculate the surface area of ??the fat cells after hematoxylin and eosin staining microscopic imaging. Results: 1 Weight: SMS2 - / - group is always light at the WT group; high-calorie diet for a long time, the greater the weight differences, 3 months SMS2 - / - < / sup> group was significantly lower than the WT group [(30.95 ± 1.7) g vs (34.45 ± 2.5) g, p lt; 0.05]. FPG: WT group of high-calorie diet for two months when FPG was significantly higher than the high-calorie diet [(7.65 ± 0.81) mmol · l -1 vs (6.06 ± 0.55) mmol · l -1 p lt; 0.05]; SMS2 - / - Group 3 FPG significantly higher than the high-calorie diet [(6.87 ± 1.44) mmol · l -1 vs (5.38 ± 1.24) mmol · l -1 , p lt; 0.05]. 3. Fins: high-calorie diet fed for three months after the WT group Fins reduced, while SMS2 - / - was significantly higher (14.05 ± 0.82) the mu · l -1 vs (12.33 ± 0.88) mu · l -1 , p lt; 0.01]. Insulin resistance assessment index (HOMA-IR): WT group of high-calorie diet for 2 months HOMA-IR was significantly higher than the high-calorie diet [(4.11 ± 0.50) vs (3.32 ± 0.48), p lt; 0.05]. High-calorie diet for the first 3 months SMS2 - / - Group HOMA-IR was significantly higher than the high-calorie diet [(4.26 ± 0.72) vs (2.95 ± 0.74), p lt; 0.05] . Plasma SM: high-calorie diet for three months SMS2 - / - group was significantly lower than WT [(3.87 ± 0.45) mg · dl -1 vs (4.26 ± 0.44) mg · dl -1 , p lt; 0.05]. ITT: of insulin load unit time blood glucose metabolic clearance rate SMS2 - / - group is 1.31 times the WT group, SMS2 - / - group peripheral tissue insulin sensitivity high. Glucose tolerance: the high-calorie diet, the glucose tolerance of two groups of mice were normal. WT group glucose load in the three months after the feeding of the high-calorie feed at 2h glucose was significantly higher than fasting [(2.22 ± 0.17) mmol · l -1 vs (1.86 ± 0.22) mmol · l - / - Group sugar load after 15min secretion of insulin ,30-60min lower average increased 3.4% , late insulin secretion increased compensatory. 9 linear regression analysis: WT group and SMS2 - / - plasma SM concentration group significant impact early blood glucose levels after glucose loading by the regression equation. 10. Adipocyte size: epididymal adipose paraffin sections of hematoxylin and eosin staining, microscopic imaging cell surface area, SMS2 - / - group was significantly less than the WT group [(343.74 ± 50.44) μm2vs. ( 670.88 ± 54.65) μm2, p lt; 0.01]. Conclusion: WT groups of mice: high-calorie diet for 3 months after the impaired obesity merger glucose tolerance and peripheral insulin sensitivity decreases. 2. SMS2 - / - mice: a high-calorie diet and after 3 months, underweight, normal glucose tolerance, normal insulin secretion, insulin sensitivity. To sum up, the further development of the WT mice serious type 2 diabetes; SMS2 - / - mice is still in the control of insulin on glucose regulation. Step SMS2 gene deletion can slow down the process of diabetes.
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