U995-LIRIC-Lille Inflammation Research International Center, University Lille, Inserm, CHU Lille, Lille, France.
VF Bioscience SAS, Loos-lez-Lille, France.
Diabetes Metab Res Rev. 2019 Feb;35(2):e3103. doi: 10.1002/dmrr.3103. Epub 2019 Jan 7.
Early (furosine) and advanced (carboxymethyllysine, CML) products of glycation (AGEs) have been reported as increased in plasma, tissues, and organs of diabetic people, indicating a direct link between glycation and type 2 diabetes (T2D). While murine models present some of the characteristics observed in diabetic humans, their pertinence as models of glycation, particularly for T2D, remains poorly described. The aim of this study was to characterize and compare glycation in several organs of two commonly studied murine models of T2D using stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS).
Defining parameters of type 2 diabetes including body weight, fasting glycaemia, and glucose intolerance were measured in three different C57BL6 mouse models of T2D-the genetic LepR (db/db) model and two diet-induced obesity (DIO) models-and their respective controls. Furosine, free, and protein-bound CML were quantified in kidneys, lungs, heart, and liver by LC-MS/MS.
The obesity, hyperglycaemia, and glucose intolerance in db/db mice was accompanied by an increase of furosine and protein-bound CML levels in all organs relative to controls. The DIO models took several months to become obese, exhibited less severe hyperglycaemia and glucose intolerance, while glycation products were not significantly different between these groups (with the exception of furosine in liver and CML in lungs).
The db/db model better reflected the characteristics of human T2D compared with the DIO models and exhibited greater formation and accumulation of both furosine and protein-bound CML in all of the organs tested here.
已报道糖尿病患者的血浆、组织和器官中早期（呋塞米）和晚期（羧甲基赖氨酸，CML）糖基化产物（AGEs）增加，这表明糖化与 2 型糖尿病（T2D）之间存在直接联系。虽然鼠模型具有一些在糖尿病患者中观察到的特征，但它们作为糖化模型的相关性，特别是对于 T2D，仍描述不足。本研究的目的是使用稳定同位素稀释液相色谱串联质谱（LC-MS/MS）来描述和比较两种常用的 T2D 鼠模型的几种器官中的糖化作用。
在三种不同的 C57BL6 T2D 鼠模型-遗传 LepR（db/db）模型和两种饮食诱导肥胖（DIO）模型及其各自的对照中，测量了体重、空腹血糖和葡萄糖耐量等 T2D 的定义参数。通过 LC-MS/MS 定量测定肾脏、肺、心脏和肝脏中的呋塞米、游离和蛋白结合 CML。
db/db 小鼠肥胖、高血糖和葡萄糖不耐受伴随着所有器官中呋塞米和蛋白结合 CML 水平相对于对照的增加。DIO 模型需要数月时间才变得肥胖，表现出较轻的严重高血糖和葡萄糖不耐受，而这些组之间的糖化产物没有显著差异（除了肝脏中的呋塞米和肺中的 CML）。
与 DIO 模型相比，db/db 模型更好地反映了人类 T2D 的特征，并且在所有测试的器官中均表现出更高的形成和积累两种呋塞米和蛋白结合 CML。
