Premium
An improved nongenetic mouse model for type 2 diabetes
Author(s) -
Gilbert Elizabeth Ruth,
Fu Zhuo,
Liu Dongmin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.783.12
Subject(s) - endocrinology , medicine , islet , insulin resistance , streptozotocin , type 2 diabetes , insulin , diabetes mellitus
The objective of this study was to generate an improved non‐genetic mouse model of type 2 diabetes (T2D). Ninety‐six 6 mo.‐old C57BL/6N males were assigned to 1 of 12 groups including 1) low‐fat diet (LFD; low‐fat control; LFC), 2) LFD with 1 i.p. 40 mg/kg BW steptozotocin (STZ)‐injection, 3), 4), 5), 6) LFD with 2, 3, 4 or 5 STZ‐injections on consecutive days, respectively, 7) high‐fat diet (HFD; high‐fat control; HFC), 8) HFD with 1 STZ‐injection, 9), 10), 11), 12) HFD with 2, 3, 4 or 5 STZ‐injections on consecutive days, respectively. At 4 wk post‐STZ injection, serum insulin levels were reduced ( P <0.02) in HFD‐mice administered at least 2 STZ‐injections as compared with HFC, but levels were not different among respective LFD groups. Glucose tolerance in mice that consumed HFD and received 2, 3 or 4 injections of STZ was greatly impaired as compared with respective LFD groups ( P < 0.05). Insulin sensitivity in HFD‐fed mice was reduced ( P < 0.05) compared to LFD‐fed mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50 % in mice that received 3 STZ‐injections. Thus, the combination of HFD and three 40 mg/kg STZ‐injections was suitable for inducing a diabetic mouse model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β‐cell mass and function.