Search bioRxiv⌕ Search

Biology subjects

Brachs, S.

Publications and source records attributed to Brachs, S..

2 recordsLinked to original sources

Robust non-invasive detection of hyperglycemia in mouse models of metabolic dysregulation: the novel Urination Index biomarker

Blood glucose is one of the most essential parameters in metabolic research. Yet, accurate blood glucose monitoring in mouse models of diabetes is challenging due to the significant stress associated with the measurements and the variability in diabetes development among experimental mouse models. This variability necessitates frequent blood glucose measurements, which only provide intermittent data and may not accurately reflect continuous metabolic changes. To address these issues, we have utilized the Tecniplast DVC system to monitor bedding moisture, enabling the detection of increased urination (polyuria), a primary symptom of diabetes. Polyuria is a hallmark of (undiagnosed/untreated) diabetes, and we revealed high correlations between bedding moisture and blood glucose during hyperglycemia. Thus, our developed algorithm enhances animal welfare by reducing the need for invasive blood glucose tests and enabling non-invasive, continuous assessment of hyperglycemia onset, progression, and severity directly within the mices home cage. Continuous monitoring of polyuria allows detailed analysis of temporal and circadian urination patterns and enables assessment of the efficacy of glucose-lowering interventions, which is crucial in developing new pharmacological treatments. We propose that this innovative approach of a novel digital biomarker, the Urination Index (UI), offers a significant advance in the methodology for diabetes research in mouse models, improves animal welfare by reducing the need for invasive blood glucose tests, and enhances the reliability of data and the quality of life for the animals involved.

physiology↗

Distinct housing conditions reveal a major impact of adaptive immunity on the course of obesity-induced type 2 diabetes

Obesity is associated with adipose tissue inflammation, insulin resistance and the development of type 2 diabetes. However, our knowledge is mostly based on conventional murine models and promising pre-clinical studies rarely translated into successful therapies.\n\nThere is a growing awareness of the limitations of studies in laboratory mice, housed in abnormally hygienic specific pathogen-free (SPF) conditions, as relevant aspects of the human immune system remain unappreciated. Here, we assessed the impact of housing conditions on adaptive immunity and metabolic disease processes during high-fat diet. We therefore compared diet-induced obesity in SPF mice with those housed in non-SPF, so called \"antigen exposed\" (AE) conditions. Surprisingly, AE mice fed a high-fat diet maintained increased insulin levels to compensate for insulin resistance, which was reflected in islet hyperplasia and improved glucose tolerance compared to SPF mice. In contrast, we observed higher proportions of effector/memory T cell subsets in blood and liver of high-fat diet AE mice accompanied by the development of nonalcoholic steatohepatitis-like liver pathology. Thus, our data demonstrate the impact of housing conditions on metabolic alterations. Studies in AE mice, in which physiological microbial exposure was restored, could provide a tool for revealing therapeutic targets for immune-based interventions for type 2 diabetes patients.

immunology↗