BACKGROUND: 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). METHODS: 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 LepRdb/db (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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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 diabetichumans, 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). METHODS: 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 LepRdb/db (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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Raquel Vieira; Selma B Souto; Elena Sánchez-López; Ana López Machado; Patricia Severino; Sajan Jose; Antonello Santini; Amelia M Silva; Ana Fortuna; Maria Luisa García; Eliana B Souto Journal: J Clin Med Date: 2019-08-28 Impact factor: 4.241