Influence of NNT mutation on glucose homeostasis in C57BL/6 mice

Abstract

Objective To explore the effect of nicotinaide nucleotide transhydrogenase(NNT) mutation on glucose homeostasis in C57BL/6 mice with mix background. Methods We generated wild type NNT homozygous, mutant NNT homozygous and heterozygous by mating the C57BL/6J (with NNT mutation) and 6N (without NNT mutation). At the age of 4 weeks, those mice were randomly assigned to normal control diet(NCD) or high-fat diet(HFD) for 4 weeks. The body weight was measured every week. At the age of 8 weeks, an intraperitoneal glucose tolerance test(IPGTT) and an intraperitoneal insulin tolerance test (ITT) were performed. Results The body weight growth was not affected by NNT mutation during an HFD fed. NNT mutant mice showed significant glucose intolerance. After 4 weeks of high fat diet, the NNT mutant mice showed a decreased insulin sensitivity, while the glucose excursion curve was not elevated in the heterozygous mice. Conclusion NNT mutation had a significant influence on the phenotype of glucose metabolism and insulin resistance of mice, in particular under a metabolic stress. The phenotypes of heterozygous and homozygous mutant ones differed from each other. When using mice with C57BL/6J and C57BL/6N mixed background in research, NNT mutation should be carefully screened in all metabolic studies. (Chin J Endocrinol Metab, 2017, 33: 673-679) Key words: NNT; HFD; Glucose tolerance; C57BL/6 mice