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Construction of a mouse model of type 2 diabetes induced by high fat diet alone and evaluation of pathological changes

YU Chen-Ge¹, HUANG Jing¹, XI Yan¹, LAI En-Yin², CHEN Su¹, XU Nan^1,*

¹School of Basic Medical Sciences, Henan University, Kaifeng 475000, China；²School of Basic Medical Sciences, Zhejiang University, Hangzhou 310000, China

Abstract

The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects of HFD on the pathology and function of organs related to glucose and lipid metabolism. C57BL/6 mice were fed with normal diet (NC group) or HFD (HFD group). The time of successful T2DM modeling was evaluated by measuring body weight, fasting blood glucose and glucose tolerance at time points of 0, 4, 8, 12, 16 and 20 weeks. The functional and pathological changes of glucose and lipid metabolism related organs were evaluated by detecting insulin tolerance, plasma lipid levels, vascular function, as well as HE staining of pancreas and liver. The results showed that compared with the NC group, the HFD group had significantly increased body weight after 8 weeks of HFD. After 16 weeks of HFD, the HFD group exhibited impaired fasting glucose tolerance. After 20 weeks of HFD, the HFD group mice reached diabetic state, showing impaired glucose tolerance and insulin resistance, islet volume reduction and vacuolar degeneration; Large number of lipid droplets appeared in liver cells, and the level of AMPK phosphorylation in liver tissue was significantly increased in the HFD groups, compared with the NC group; There was endothelial dependent diastolic dysfunction in the thoracic aorta of the HFD group; Compared with the NC group, the HFD group mice showed a significant increase in urinary protein levels. These results suggest that T2DM mouse model can be successfully established by HFD induction alone for 20 weeks. The model is characterized by insulin resistance, fatty liver, hyperlipidemia, vascular dysfunction, renal dysfunction and pathological changes of islet and liver cells, which are similar to those of T2DM patients. Therefore   it can be used as an ideal animal model for T2DM research.

Key words: type 2 diabetes mellitus; high fat diet; insulin resistance; fatty liver

Received: 　　Accepted:

Corresponding author: 徐楠　　E-mail:

DOI: 10.13294/j.aps.2024.0003

Citing This Article：

YU Chen-Ge, HUANG Jing, XI Yan, LAI En-Yin, CHEN Su, XU Nan. Construction of a mouse model of type 2 diabetes induced by high fat diet alone and evaluation of pathological changes. Acta Physiol Sin 2024; 76 (3): 385-393 (in Chinese with English abstract).