Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy

被引:17
作者
Norgaard, Sisse A. [1 ,2 ,3 ]
Sand, Fredrik W. [1 ]
Sorensen, Dorte B. [2 ]
Abelson, Klas S. P. [4 ]
Sondergaard, Henrik [3 ]
机构
[1] Novo Nordisk AS, Diabet & Cardiovasc Pharmacol, Novo Nordisk Pk 1, DK-2760 Malov, Denmark
[2] Univ Copenhagen, Dept Vet Dis Biol, Copenhagen, Denmark
[3] Novo Nordisk AS, Diabet Complicat Pharmacol, Bagsvaerd, Denmark
[4] Univ Copenhagen, Dept Expt Med, Copenhagen, Denmark
关键词
streptozotocin-induced diabetes; diabetic nephropathy; weight loss; refinement; reduction; RODENT MODELS; STRESS; MICE; HYPERGLYCEMIA; METABOLISM; INDICATORS; EXCRETION; APOPTOSIS; INSULITIS; HORMONES;
D O I
10.1177/0023677217747915
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight toss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we demonstrated that diabetic male mice receiving softened chow had reduced acute weight toss following STZ treatment (p= 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice without this supplement reached this humane endpoint (p=0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow (p= 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.
引用
收藏
页码:373 / 383
页数:11
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