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FBP 90194 Scientific Reports 9(1)_14588 - TNie et al 101019.pdf (2.46 MB)

Altered metabolic gene expression in the brain of a triprolyl-human amylin transgenic mouse model of type 2 diabetes

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posted on 2023-05-03, 19:18 authored by Tina Nie, Shaoping Zhang, Greeshma Amarsingh, Hong Liu, Mark McCann, Garth Cooper
Type 2 diabetes mellitus is a major health concern worldwide; however, the molecular mechanism underlying its development is poorly understood. The hormone amylin is postulated to be involved, as human amylin forms amyloid in the pancreases of diabetic patients, and oligomers have been shown to be cytotoxic to β-cells. As rodent amylin is non-amyloidogenic, mice expressing human amylin have been developed to investigate this hypothesis. However, it is not possible to differentiate the effects of amylin overexpression from β-cell loss in these models. We have developed transgenic mice that overexpress [25, 28, 29 triprolyl]human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 model. This model allows us to investigate the effects of chronic overexpression of non-cytotoxic amylin. We characterised this model and found it developed obesity, hyperglycaemia and hyperinsulinaemia. This phenotype was associated with alterations in the expression of genes involved in the amylin, insulin and leptin signalling pathways within the brain. This included genes such as c-Fos (a marker of amylin activation); Socs3 (a leptin inhibitor); and Cart, Pomc and Npy (neuropeptides that control appetite). We also examined Socs3 protein expression and phosphorylated Stat3 to determine if changes at the mRNA level would be reflected at the protein level.

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Language

  • English

Does this contain Māori information or data?

  • No

Publisher

Springer Nature

Journal title

Scientific Reports

ISSN

2045-2322

Citation

Nie, T., Zhang, S., Amarsingh, G. V., Liu, H., McCann, M. J., & Cooper, G. J. S. (2019). Altered metabolic gene expression in the brain of a triprolyl-human amylin transgenic mouse model of type 2 diabetes. Scientific Reports, 9, 14588. doi:10.1038/s41598-019-51088-x

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