Blood Glucose Profiles Of Diabetic NOD Mice Treated With Insulin Glargine And Aspart, As Well As Their Effects On Insulitis And Islet Bcl-2/Bax Expression

Objective:To evaluate insulin glargine and aspart for their ability to normalize the blood glucose profile of diabetic NOD mice with different dose. Besides, investigate the effects of early intensive insulin therapy on insulitis, apoptosis, regeneration of islets.Methods:Trial 1:Thirty newly diagnosed diabetic female NOD mice were randomized into A,B,C,D,E 5 groups(each group n=6). Group A, B, C and D had free access to food and they were given insulin glargine(IG) at 9:00 subcutaneously in different doses:100IU/(kg·d),50IU/(kg-d),15IU/(kg-d) and PBS 5μL/d respectively. Group E was the intensive insulin therapy group: Insulin glargine as a basal replacement was administrated subcutaneously at 9:00, and food was given for one hour after insulin aspart(IA) administrated subcutaneously every four hours(begun at 03:00 per day).Also a group (Group F,n=6) of age matched non-diabetic NOD mice was included in the study. The blood glucose value at different time on the fourth day(24h) were recorded and the effect of each treatment was estimated on the 15th day.Trial 2:Twelve newly diagnosed diabetic female NOD mice were randomiz-ed into 2 groups:intensive insulin therapy group (Ⅰ,n=6) and PBS group (Ⅱ, n=6),The treatments of these two groups were initiated within 3 days after onset of diabetes. Also a PBS control group (III,n=6) of age matched non-diabetic mice was included in the study. The approach, dose and time of insulin/PBS ad-ministrated was in accordance with Trial 1,group E,D,C respectively. Group II was sacrificed on the 20th day while the other two groups were killed after 60 days of treatment. Pancreases were removed to examine insulitis scores by HE straining, and expression of Bcl-2 and Bax on islet cells were detected by immunohistochemical straining.Results:1. The average blood glucose was significantly lower in intensive insulin therapy group E with IA preprandially plus basal IG than in Group B,C and D. [respectively (6.99±1.28)mmol/L vs (10.78±3.36)mmol/L, (14.66±3.84) mmol/L and (22.83±1.32)mmol/L,P<0.05]. But there was no significant difference when Group E Compared with Group A and Group F (P>0.05).2. The fluctuation of blood glucose value in Group E (9.91±3.28)mmol/L was significantly lower when compared with other insulin glargine groups[Group A (17.63±4.09) mmol/L, GroupB (20.53±7.17) mmol/L, and Group C (20.08±5.31) mmol/L, P<0.01 respectively].3.The percentage of normal blood glucose during 24 hours in intensive insulin therapy group E (67%) was also much higher than Group A,B,C (38%,33%,33%)4.Diabetic symptom was under control. But severe persistent hypoglycemia were often observed in those high dose single insulin glargine groups.By the time of the 15th day, The death rate of Group A,B,C,E was 5/6,3/6,0/6,0/6 respectively because of hypoglycemia.5. The mean weight (21.6±1.1)gand insulitis score (1.67±0.80) of intensive group I were significant lower than that in group II (P<0.05), and there was no significant difference when compared with groupIII (P=0.12,0.55, respectively).6. The expression of Bcl-2 on islet cells was stronger in intensive insulin therapy group than in the other two groups(P< 0.05). The Bax expression was stronger in intensive insulin therapy group than in groupIII(P< 0.05), but there was no significant difference when compared with group II (P=0.26).Conclusions:1. It's better to control diabetic NOD mice blood glucose by intensive insulin therapy than by only once daily long acting insulin glargine administrat-ion based on the average blood glucose, blood glucose fluctuates and the percentage of normal blood glucose during 24 hours.2.Early intensive insulin therapy can decrease insulitis of Langerhans, increase the expression of Bcl-2 and decrease the expression of Bax on islet.