Mechanisms of muscle insulin resistance

This project formed part of Ana's PhD where we investigated the mechanisms of lipid-induced insulin and anabolic resistance in skeletal muscle myotubes and in humans.

In vitro work elucidated novel roles of extracellular ATP as an anabolic signalling molecule able to activate insulin and mTOR signalling pathways and enhance glucose uptake and metabolism in myotubes. Contrary to the initial hypothesis, extracellular ATP did not contribute to the inflammation and insulin resistance caused by treatment with high concentrations of saturated fatty acids. We aim to explore the role of purinergic receptors in the control of glucose homeostasis in health and disease.

In humans, we, in collaboration with Dr. Benjamin Wall and Dr. Marlou Dirks at Exeter Sport and Health Sciences, investigated the impact of increased lipid availability on disuse-induced insulin and anabolic resistance. We concluded that two days of immobilisation (forearm cast) is sufficient to cause substantial muscle insulin resistance, not aggravated by high fat overfeeding, and that 7 days of immobilisation impairs the ability of a protein-rich meal to promote positive amino acid balance, in a manner that is aggravated by high fat overfeeding. The outcome of this work can be found in Dirks et al., 2020 and Wall et al., 2020 (below).