The LepR^db/db mice model for studying glycation in the context of diabetes

Abstract

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.

The Effect of Lactobacillus fermentum ME‐3 Treatment on Glycation and Diabetes Complications

“…In this study, the Lactobacillus fermentum ME‐3 bacterial strain was tested for its capacity to ameliorate glycemic control, reduce the formation, and accumulation of glycation products, and prevent or attenuate the development of T2D‐induced complications. The diabetic phenotype was here represented by the hyperphagic LepR db/db animals, selected in a previous study, [ 31 ] which were both obese and hyperglycemic throughout the experiment.…”

“…Sample preparation for free CML and protein‐bound CML analysis, adapted from Niquet‐Léridon and Tessier, [ 30 ] is also described elsewhere. [ 31 ] To separate free CML from protein‐bound CML, a second 10 mg aliquot of the lyophilized, powdered organ, or 25 µL plasma was solubilized for 30 min on ice in 200 or 12.5 µL 10% TCA, respectively, to precipitate proteins. After centrifugation (21 000 × g , 10 min, 4 °C), supernatants (free CML) were separated from the proteinaceous pellets (protein‐bound CML).…”

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

“…However, much work is still required to identify the physiological role of H19 in lipid metabolism in skeletal muscle. To study the specific role of H19 in the pathology underlying insulin resistance, we used db/db mice as our model, which are widely used to study type 2 diabetes and obesity [ 26 – 28 ]. Our analysis further clarifies the role of H19 in lipid metabolism in skeletal muscle and its connection to insulin resistance.…”

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

“…However, much work is still required to identify the physiological role of H19 in lipid metabolism in skeletal muscle. To study the speci c role of H19 in the pathology underlying insulin resistance, we used db/db mice as our model, which are widely used to study type 2 diabetes and obesity (26)(27)(28). Our analysis further clari es the role of H19 in lipid metabolism in skeletal muscle and its connection to insulin resistance.…”