胃袖带切除术对GK大鼠2型糖尿病的影响及其机理

目的研究胃袖带切除术（sleevegastrectomy，SG）对GK大鼠2型糖尿病（type2diabetesmellitus，T2DM）的治疗作用及其可能机理。方法将13只12周龄的GK大鼠随机分为2组：SG组7只和假手术组（SO组）6只，分别行SG术和假手术。于术前及术后1、4、10和26周测量2组大鼠的体质量、24h进食量、空腹血糖值、血清胰高血糖素样肽-1（glucagon-likepeptide-1，GLP-1）和血清生长激素释放肽（Ghrelin）浓度；于术后10周检测2组大鼠的粪便能量含量，并进行口服葡萄糖耐量实验（OGTT）和胰岛素耐受性实验（ITT）。结果①体质量：各时点2组大鼠的体质量比较差异均无统计学意义（P〉0．05）；与术前比较，术后1周2组大鼠的体质量均降低（P〈0．01），术后10和26周的体质量均增加（P〈0．01）。②24h进食量：与SO组比较，术后4和10周SG组大鼠的24h进食量均较低（P〈0。05）。与术前比较，SG组大鼠术后1、4及10周的进食量均较低（P〈0．05），SO组大鼠术后1周的进食量低于术前（P〈0．05）。③空腹血糖值：与SO组比较，术后各时点SG组大鼠的空腹血糖值均较低（P〈0．01）。与术前比较，SG组大鼠术后各时点的空腹血糖值均较低（P〈0．01），而SO组大鼠仅术后1周明显低于术前∽〈0．OD。④血清GLP-1水平：与SO组比较，术后4、10及26周SG组大鼠的血清GLP．1水平均较高（P〈0．05）。与术前比较，术后4、10及26周SG组大鼠的血清GLP-1水平较高（P〈0．05），而术后SO组大鼠的血清GLP．1水平无明显变化（P〉0．05）。⑤血清Ghrelin水平：与SO组比较，术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．01）。与术前比较，术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．001），而SO组大鼠的血清Ghrelin水平无明显变化（P〉0．05）。⑥曲线下面积（AUC）：SG组大鼠的AUC（OGTT和ITT）均较SO组低（P〈0．01）。结论SG术可以明显降低GK大鼠的空腹血糖值，改善葡萄糖耐量及增强胰岛素敏感性，该作用可能是GLP．1、Grelin等多种胃肠道激素共同作用的结果。SG术可能是潜在的非肥胖型T2DM的治疗方法。

Effect and Mechanism of Sleeve Gastrectomy for Type 2 Diabetes Mellitus in GK Rats

Objective To explore the effect and mechanism of sleeve gastrectomy （SG） for type 2 diabetes mellitus （T2DM） in Goto-Kakizaki （GK） rats. Methods Thirteen male GK rats at 12 weeks of age were randomly divided into SG group （n=7） and sham operation group （SO group, n=6）, receiving SG surgery and sham operation respectively. Body weight, food intake in 24 hours, fasting plasma glucose, plasma glucagon-like peptide-1 （GLP-1）, and plasma Ghrelin of rats in 2 groups were measured or tested before operation, 1, 4, 10, and 26 weeks after operation. In 10 weeks after operation, fecal energy content of rats in 2 groups was tested, in addition, oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed to investigate the glucose tolerance and insulin sensitivity. Results @ Body weight： there were no significant difference on body weight between the 2 groups （P〉 0. 05）. Compared with time point of before operation, the body weight of both 2 groups decreased in 1 week after operation （P〈 0. 01）, but increased in 10 weeks and 26 weeks （P〈 0.01）. @ Food intake in 24 hours： compared with SO group, the food intake of SG group were lower in 4 weeks and 10 weeks after operation （P 〈 0.05）. Compared with time point of before operation, the food intake of SG group were lower in 1, 4, and 10 weeks after operation （P〈0. 05）, but lower only in 1 week in SO group （P 〈 0.05）. @ Value of fasting glucose ： compared with SO group, the value of fasting glucose in SG group were lower after operation （P 〈 0.01）. Compared with time point of before operation, the value of fasting glucose of SG group were lower after operation （P〈 0.01）, but decreased in 1 week only in SO group （P〈 0. 01）. @ Level of serum GLP-1 ： compared with SO group, the levels of serum GLP-1 in SG group were higher in 4, 10, and 26 weeks after operation （P〈0.05）. Compared with time point of before operation, the levels of serum GLP-1 in SG group were higher in 4, 10, and 26 weeks after operation （P〈0.05）, but levels of serum GLP-1 in SO group didn＇t change significantly （P〉 0.05）. @Level of serum Ghrelin： compared with SO group, the levels of serum Ghrelin in SG group were lower at all time points after operation （P〈 0. 01）. Compared with time point of before operation, the levels of serum Ghrelin in SG group were lower at all time points after operation （P〈0. 001）, but levels of serum Ghrelin in SO group didn＇t change significantly （P〉 0. 05）. @ Areas under curves （AUC） ： the AUC of OGTT and ITT test in SG group were both lower than those of SO group （P〈0. 01）. Conclusion SG surgery can induce the level of fasting plasma glucose, and can improve glucose tolerance and insulin sensitivity with significant changes of levels of plasma GLP-1 and Ghrelin, sugg- esting that SG surgery may be a potential strategy to treat patient with T2DM but without obesity or insulin resistance.