Computational identification of disease models through cross-species phenotype comparison.

The use of standardised phenotyping screens to identify abnormal phenotypes in mouse knockouts, together with the use of ontologies to describe such phenotypic features, allows the implementation of an automated and unbiased pipeline to identify new models of disease by performing phenotype comparisons across species. Using data from the International Mouse Phenotyping Consortium (IMPC), approximately half of mouse mutants are able to mimic, at least partially, the human ortholog disease phenotypes as computed by the PhenoDigm algorithm. We found the number of phenotypic abnormalities in the mouse and the corresponding Mendelian disorder, the pleiotropy and severity of the disease, and the viability and zygosity status of the mouse knockout to be associated with the ability of mouse models to recapitulate the human disorder.

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism.

Objective: SGLT2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may be metabolic adaptations due to urinary glucose loss. Here, we investigated the cellular and molecular effects of 5 weeks of dapagliflozin treatment on skeletal muscle metabolism in type 2 diabetes patients.

Methods: Twenty-six type 2 diabetes mellitus patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out.