Abstract: Objective To analyze the biochemical and pathological changes in mice with type 2 diabetes mellitus (T2DM)
induced by high-fat diet combined with low-dose streptozotocin (STZ) injections. Methods C57BL/6J mice were divided
randomly into normal control group (NC group), high-fat diet group (HC group) and high-fat diet plus STZ group (HC+STZ
group). The mice were fed on normal chow or a high-fat diet for 1 month before two introperitoneal injections of STZ (40 mg/
kg) or citrate buffer with an interval of 24 h as appropriate. Fasting blood glucose (FBG) was detected every week for 4 weeks,
and oral glucose tolerance test (OGTT) was performed one month after the injections, after which the biochemical profiles, islet
and liver were evaluated by immunohistochemical and pathological analysis. Results In HC+STZ group, FBG was above the
cutoff value (13.89 mmol/L) in 75% of the mice at 1 week after STZ injections and in all the mice at two weeks except for the
death of 1 mouse, with a success rate of modeling of 91.3%. FBG in HC group, though slightly higher than that in NC group,
remained normal (6.8 mmol/L). The body weight in HC+STZ and HC groups was significantly higher than that in NC group
after feeding but without obvious increases after the injections (P<0.01). Blood glucose in HC+STZ group at 0.5 to 2 h after
OGTT and the area under curve (AUC) were higher than those in NC and HC groups (P<0.01); the AUC in HC group was a
also higher than that in NC group (P<0.05). Plasma creatinine was significantly higher in HC+STZ group than in NC (P<0.01)
and HC (P<0.05) groups. Insulin secretion by the islets decreased obviously in HC+STZ and HC group. The mice in HC+STZ
group showed atrophy, fibrosis, and vacuolization in the islets with mild fatty liver but no visible renal pathologies.
Conclusion High-fat diet and low-dose STZ injections can induce T2DM in mice with very similar biochemical and
pathological changes to human T2DM and with such complications as fatty liver.