Feasibility of C57BL/Ksj db/+ mice used as the model of gestational diabetes mellitus

Abstract

Objective To identify the glycometabolism features ofC57BL/Ksj db/+ mice at gestational period and provide the evidence for the mice used as the animal model of gestational diabetes mellitus (GDM).Methods Ten C57BL/Ksj db/+ female mice and ten wild female mice were randomly selected and mated with wild male mice respectively.Day 3 before mating,days 6,11 and 17 of pregnancy,and day 6 after delivery represented pre pregnancy,early-pregnancy,mid-pregnancy,late-pregnancy and post-pregnancy periods,respectively.The levels of glucose tolerance and fasting insulin of female mice were compared at progestation,different gestational periods and puerperium between the two groups.Days 6,11,14,17 and 20 (before labor) of pregnancy served as five time-points of pregnancy,leptin levels of female mice of the two groups were dynamically monitored during pregnancy,and analyzed at different gestational ages.The data were analyzed by Tukey test of one-way ANOVA.Results (1) Compared with the normal pregnant mice,the levels of glucose tolerance of C57BL/Ksj db/+ female mice were significantly decreased,while the levels of fasting insulin were dramatically increased with the progression of pregnancy [day 6 of pregnancy,(8.6 ± 0.6) mU/L vs (7.5 ±1.1) mU/L; day 11 of pregnancy,(9.8±0.6) mU/L vs (8.5± 1.1) mU/L; day 17 of pregnancy,(10.4±0.8) mU/L vs (9.9±0.5) mU/L; t=1.859,4.056 and 3.078,P=0.085,0.000 and 0.000] and recovered to the pre-pregnancy level after delivery.(2) The level of leptin in serum of C57BL/Ksj db/+ pregnant mice was significantly higher than that at non-pregnant period [pre-pregnancy and days 6,11,14,17 and 20 of pregnancy:(911.0±238.8) ng/L,(1 342.2± 132.3) ng/L,(1 821.9±238.2) ng/L,(1 816.3± 142.3) ng/L,(1 752.4± 126.6) ng/L,and (1 926.4±61.6) ng/L,respectively; t=3.887,8.210,8.161,7.585 and 9.153,P=0.005,0.000,0.000,0.000 and 0.000],but showed no apparent change with the gestational ages after mid-gestation.Conclusion Changes of glycometabolism and the levels of leptin and insulin of C57BL/Ksj db/+ pregnant mice during pregnancy are similar to those of GDM patients,the levels of fasting insulin are dramatically increased with the progression of pregnancy,and return to normal after delivery,the level of leptin is higher than that at non-pregnant period,but is not correlated with the gestational ages.C57BL/Ksj db/+ pregnant mice can be used as the animal model of GDM. Key words: Diabetes, gestational; Disease models, animal; Blood glucose; Leptin; Mice,inbred C57BL