小鼠器官切片染色中可以看到只有胰脏(最左)中有IAPP的积聚,肝、肾、骨骼肌和心脏中都不存在
研究人员表示,他们的研究提供了IAPP错误折叠并积聚在II型糖尿病中的重要作用,因为在没有其他影响因素,如高脂饮食、肥胖或胰岛素信号传导中断的情况下,它的存在足以诱导糖尿病的发生[7]。
此外,他们认为这个研究成果的重要性不仅仅局限于了解疾病的起源和进程,还为防止疾病的发展和治疗提供了新的靶点,例如防止IAPP积聚或是清除IAPP积聚物的药物可能会阻止所在胰岛的损伤,也防止积聚物扩散到其它胰岛,帮助控制、稳定患者的病情。
Soto教授透露,下一步他们想要研究糖尿病是否可以通过已知的朊病毒传播方式,如输血或是器官移植来传播[1],尽管在器官移植后发生糖尿病[8]已经有过一些报道了,但是是否是通过IAPP却是完全未知的。而且他表示,如果资金支持允许的话,他们还希望能继续进行非人类的灵长类动物实验,这对于将这一原理投射到人体内会起到重要的作用。
参考资料:
[1] http://www.sciencemag.org/news/2017/08/could-diabetes-spread-mad-cow-disease
[2] Inductionof IAPP amyloid deposition and associated diabetic abnormalities by aprion-like mechanism. Journal of Experimental Medicine, 2017, DOI: 10.1084/jem.20161134
[3] Westermark, P. 1972. Quantitative studies on amyloid in the islets of
Langerhans. Ups. J. Med. Sci. 77:91–94.
[4] Novials, A., I. Rojas, R. Casamitjana, E.F. Usac, and R. Gomis. 2001. A novel
mutation in islet amyloid polypeptide (IAPP) gene promoter is associated
with type II diabetes mellitus. Diabetologia. 44:1064–1065.
[5] Janson, J., W.C. Soeller, P.C. Roche, R.T. Nelson, A.J. Torchia, D.K. Kreutter,
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[6] Clark, A., C.A. Wells, I.D. Buley, J.K. Cruickshank, R.I. Vanhegan, D.R.
Matthews, G.J. Cooper, R.R. Holman, and R.C. Turner. 1988. Islet amyloid,
increased A-cells, reduced B-cells and exocrine fibrosis: quantitative
changes in the pancreas in type 2 diabetes. Diabetes Res. 9:151–159.
[7] http://www.genengnews.com/gen-news-highlights/transmission-of-diabetes-prion-like-aggregates-triggers-disease-symptoms/81254744
[8] Marchetti P. New-onset diabetes after transplantation[J]. The Journal of heart and lung transplantation, 2004, 23(5): S194-S201.