Comparatively analyzing the liver-specific transcriptomic profiles in Kunming mice afflicted with streptozotocin- and natural food-induced type 2 diabetes mellitus

• Published in: Molecular biology reports Vol. 49; no. 2; pp. 1369 - 1377
• Main Authors: Wu, Yanjun, Zhu, Xiangxing, Odiba, Arome Solomon, Lin, Zisheng, Wen, Jiancong, Gong, Daoyuan, Liang, Jing, Wu, Shuguang, Lan, Ganqiu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2022; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animal models; Animals; Animals, Outbred Strains - genetics; Biomedical and Life Sciences; Blood Glucose - metabolism; Carbohydrates; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diet; Diet, High-Fat; Disease Models, Animal; Gene Expression - genetics; Gene Expression Profiling - methods; Genomes; High carbohydrate diet; High fat diet; Histology; Insulin - metabolism; Life Sciences; Liver; Liver - pathology; Male; Metabolism; Mice - genetics; Morphology; Nutrient deficiency; Organ Specificity - genetics; Original Article; p53 Protein; Streptozocin; Streptozocin - pharmacology; Transcription; Transcriptome - genetics; Transcriptomes; Transcriptomics; Kunming mice; Animal model; Transcriptome analysis; Type 2 diabetes mellitus (T2DM); Streptozotocin (STZ)
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06970-1

Background Streptozotocin is a classic drug used to induce diabetes in animal models. Objective The aim of this study is to investigate the liver transcriptome of Kunming mice with diabetes induced by either streptozotocin (STZ) or Non-STZ. Methods Forty male mice were randomly assigned into four groups: Control (Ctr, standard diet), mHH (high fat and high carbohydrate diet), mHS (high fat and high carbohydrate diet for 4 weeks followed by 60 mg/kg STZ for 3 consecutive days) and mSH (60 mg/kg STZ for 3 consecutive days followed by a high fat and high carbohydrate diet for 12 weeks). All mice injected with STZ were identified as diabetic despite the sequential feeding of high fat and high carbohydrate diets. Results Only 7 of 13 mice in the mHH group met the diagnostic criteria for diabetes. The asting blood glucose (FBG) of the mHH, mHS, mSH and Ctrl groups was 13.27 ± 1.14, 15.01 ± 2.59, 15.95 ± 4.38 and 6.28 ± 0.33 mmol/L at the 12th week, respectively. Compared with the mHH group, transcription was elevated in 85 genes in the livers of mHS mice, while 21 genes were downregulated and 97 genes were upregulated in the mSH group while 35 genes were decreased. A total of 43 co-expressed genes were identified in the mHS vs mHH and mSH vs mHH groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses showed that two corporate GO terms and two KEGG pathways were significantly annotated in the STZ-treated groups. Both the GO term and pathway were related to the metabolism mediated by p53. Conclusion A high fat and high carbohydrate diet combined with a low dose of STZ can effectively induce diabetes in Kunming mice despite the abnormal expressions of genes in the liver. The differentially expressed genes were related to metabolism mediated by p53.