胰岛素腹腔注射配合饮食干预对自发性2型糖尿病KKAy小鼠血糖调控效果的研究

Effect of insulin intraperitoneal injection combined with dietary intervention on blood glucose regulation in KKAy mice with spontaneous type 2 diabetes

目的研究胰岛素腹腔注射配合饮食干预对自发性2型糖尿病KKAy小鼠血糖调控的效果。方法建立2型糖尿病动物模型,选取健康C57BL/6J小鼠作为正常对照组,健康KKAy小鼠作为未发病组,将建模成功的KKAy小鼠随机分为皮下胰岛素治疗组、腹腔胰岛素治疗组和发病不治疗组。未发病组给予维持饲料,其他组全部采用高脂高糖饲料。每日喂养时间为08:00至20:00,间隔4 h喂养1次,共4次。皮下和腹腔胰岛素治疗组在喂养前分别进行胰岛素皮下和腹腔注射,第1次喂养前注射重组甘精胰岛素注射液(皮下组:0.125 IU/g;腹腔组:0.250 IU/g),间隔0.5 h后注射生物合成人胰岛素注射液(皮下组:0.075 IU/g;腹腔组:0.125 IU/g);其余3次喂养前,注射生物合成人胰岛素注射液(皮下组:0.075 IU/g;腹腔组:0.125 IU/g),共给药4周。定期检测各组小鼠饮食量、体质量及空腹血糖、餐后1、2 h血糖,并进行口服葡萄糖耐受实验。结果腹腔胰岛素治疗组小鼠的总饮食量低于皮下胰岛素治疗组;与初始体质量相比,第4周皮下和腹腔胰岛素治疗组体质量分别下降5.05、3.59 g;皮下和腹腔胰岛素治疗组空腹血糖变化分别为5.4~9.4、5.4~6.4 mmol/L;餐后1 h血糖变化分别为4.6~12.3、5.7~8.9 mmol/L;餐后2 h血糖变化分别为2.5~9.8、3.8~7.1 mmol/L。针对糖耐受指标,腹腔胰岛素治疗组在各时间点均有提高,皮下胰岛素治疗组除0、60 min外,其他时间点呈现下降。结论配合饮食干预,胰岛素腹腔注射相比胰岛素皮下注射,对自发性2型糖尿病KKAy小鼠血糖的控制效果更佳,且对糖耐受具有明显改善作用。

Objective To study the effect of insulin intraperitoneal administration combined with dietary intervention on glycemic regulation in in KKAy mice with spontaneous type 2 diabetes.Methods An animal model of type 2 diabetes was established,and healthy C57BL/6J mice were selected as the normal control group and healthy KKAy mice as the non-disease group.The successfully modeled KKAy mice were randomly divided into the subcutaneous group,the intraperitoneal group,and the untreated group.The non-disease group was given a maintenance diet,and all other groups were fed a high-fat,high-sugar diet.The daily feeding time was from 08:00 to 20:00,with one feeding at a 4-hour interval,for a total of four times.The subcutaneous and intraperitoneal groups were given subcutaneous and intraperitoneal insulin injections before feeding,and recombinant glargine insulin injection(subcutaneous group:0.125 IU/g;intraperitoneal group:0.250 IU/g)was injected before the first feeding,and biosynthetic human insulin injection(subcutaneous group:0.075 IU/g;intraperitoneal group:0.125 IU/g)was injected after a 0.5 h interval;the rest 3 times before feeding,the biosynthetic human insulin injection(subcutaneous group:0.075 IU/g;intraperitoneal group:0.125 IU/g)was injected for 4 weeks.The dietary intake,body mass,fasting blood glucose,and 1 and 2 h postprandial blood glucose of mice in each group were tested regularly,and an oral glucose tolerance test was performed.Results The total dietary intake of mice in the intraperitoneal group was lower than that in the subcutaneous group.Compared with the initial body mass,the body mass of the mice in the subcutaneous and intraperitoneal groups decreased by 5.05 and 3.59 g at week 4,respectively.The changes of fasting blood glucose in the subcutaneous and intraperitoneal groups ranged from 5.4 to 9.4 and 5.4 to 6.4 mmol/L,respectively,and the changes of 1 h postprandial blood glucose ranged from 4.6 to 12.3 and 5.7 to 8.9 mmol/L,respectively,and the changes of 2 h postprandial blood glucose ranged from 2.5 to 9.8 and 3.8 to 7.1 mmol/L,respectively.For the glucose tolerance index,the intraperitoneal group showed improvement at all time points,and the subcutaneous group showed a decrease at all time points except for 0 and 60 min.Conclusions In combination with dietary intervention,insulin intraperitoneal injection was more effective in controlling blood glucose in KKAy mice with spontaneous type 2 diabetes compared with subcutaneous insulin injection,and had a significant improvement in glucose tolerance.