Metabolic modeling of muscle metabolism identifies key reactions linked to insulin resistance phenotypes.

ABSTRACT:

Objective

Dysregulated muscle metabolism is a cardinal feature of human insulin resistance (IR) and associated diseases, including type 2 diabetes (T2D). However, specific reactions contributing to abnormal energetics and metabolic inflexibility in IR are unknown.

Methods

We utilize flux balance computational modeling to develop the first systems-level analysis of IR metabolism in fasted and fed states, and varying nutrient conditions. We systematically perturb the metabolic network to identify reactions that reproduce key features of IR-linked metabolism.

Results

While reduced glucose uptake is a major hallmark of IR, model-based reductions in either extracellular glucose availability or uptake do not alter metabolic flexibility, and thus are not sufficient to fully

SUBMITTER: Nogiec C 

PROVIDER: S-EPMC4338313 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature