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Updated: Oct 7, 2025
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific
Marin E Nelson1, Søren Madsen1, Kristen C Cooke1
1School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia.
Abstract:
Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.
