Characterization of db/db diabetic mice

C Duval, P Guillaume, D Provost, M Lemaire, G Froget. Porsolt SAS, 53940, France

The complexity and heterogeneity of diabetes is illustrated in the variety of available experimental models, such as genetically diabetic rodents or pharmacologically induced diabetes. Because of the polymorphism of the pathology, each model needs to be well understood.

The aim of this work is to characterize male db/db mice (C57BL/KSJRj-db), in comparison with non-diabetic lean controls (N = 9-10 per group) in respect to their diabetic profile but also associated pathological markers.

These include body weight gain, food and water intake, basal glycemia, response to glucose challenge, diuresis parameters together with intestinal motility, and also thermal and tactile sensitivity.

Body weight was significantly higher in db/db mice, as compared with controls, over the testing period between 7 and 15 weeks of age (34.2 ± 0.3 g vs. 18.2 ± 0.2 g at 7 weeks of age and 41.0 ± 1.9 vs. 22.1 ± 0.4 g at 15 weeks of age).

Food and water intakes were significantly increased in db/db mice, as compared with controls (+84%, p<0.001 for food intake and +162%, p<0.001 for water intake cumulated over 24 hours).

A marked increase in basal glycemia was observed in db/db, as compared with controls, over the testing period (e.g. 28.43 ±1.59 mmol/L vs. 11.42 ± 0.61 mmol/L, p<0.001 at 8 weeks of age).

Glycemia markedly increased shortly after oral glucose challenge (2 g/kg) in both db/db mice and their controls, but whereas controls recovered basal values within 2 hours, db/db mice did not return to basal level up to 240 minutes post-challenge.

Diuresis was significantly higher in db/db mice, as compared with controls (+0.658 g/mouse, p<0.01 for urinary volume cumulated over 6 hours).

Small intestinal transit was significantly decreased in db/db mice, as compared with controls (distance covered: -13%, p<0.05 in the charcoal test). A tendency towards a decrease was also observed on colonic transit (expulsion latency: 0h48min vs. 1h05min, ns in the bead test).

db/db mice showed a moderate hyposensitivity, as compared to controls, to tactile stimulation (force-inducing paw withdrawal: +30%, ns in the Von Frey test and +24%, p<0.01 in the pinchmeter test), but a marked hypersensitivity in response to thermal stimulation (latency to first withdrawal: -54%, p<0.001 in the cold plate test).

These findings indicate clear differences in db/db mice, as compared with non-diabetic lean mice, in respect to their diabetic profile but also to co-morbidity factors. The db/db model is therefore representative of the polymorphism of diabetes, and can be a useful tool for the pharmacological evaluation of antidiabetic drug candidates as adjunct therapies.