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1 型糖尿病小鼠的糖原结构:探索糖尿病糖原分子脆弱性的起源。

Glycogen structure in type 1 diabetic mice: Towards understanding the origin of diabetic glycogen molecular fragility.

机构信息

Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou 225009, Jiangsu Province, China.

出版信息

Int J Biol Macromol. 2019 May 1;128:665-672. doi: 10.1016/j.ijbiomac.2019.01.186. Epub 2019 Jan 29.

Abstract

Glycogen is a complex branched glucose polymer. Liver glycogen in db/db mouse, a type-2 diabetic mouse model, has been found to be more molecularly fragile than in healthy mice. Size-exclusion chromatography was employed in this study to investigate the molecular structure of liver glycogen in two types of type 1 diabetic mouse models (NOD and C57BL/6J mice), sacrificed at various times throughout the diurnal cycle, and the fragility of liver glycogen after exposure to a hydrogen-bond disruptor were tested. Type 1 diabetic mice exhibit a similar glycogen fragility with that observed for db/db mice. This eliminates many of the potential causes for glycogen molecular fragility; the most likely explanation is that it is caused by high blood-glucose level and/or insulin deficiency, both phenotypes being common to both type 1 and type 2 diabetic mice. This result suggests ways towards new drug targets for the management of diabetes.

摘要

糖原是一种复杂的分支葡萄糖聚合物。在 2 型糖尿病模型 db/db 小鼠中,已发现肝糖原的分子结构比健康小鼠更为脆弱。本研究采用排阻色谱法研究了两种 1 型糖尿病小鼠模型(NOD 和 C57BL/6J 小鼠)在整个昼夜周期的不同时间点肝糖原的分子结构,以及暴露于氢键破坏剂后肝糖原的脆弱性。1 型糖尿病小鼠表现出与 db/db 小鼠相似的糖原脆弱性。这排除了许多导致糖原分子脆弱的潜在原因;最可能的解释是它是由高血糖水平和/或胰岛素缺乏引起的,这两种表型在 1 型和 2 型糖尿病小鼠中都很常见。这一结果为糖尿病的药物治疗靶点提供了新的思路。

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