310P Stress exacerbates glucose intolerance in the mdx mouse model of Duchenne muscular dystrophy.

Loss of brain-specific dystrophin has been implicated in the heightened predisposition of patients and vertebrate models of Duchenne muscular dystrophy (DMD) to stressful stimuli. Using 18F-fluorodeoxyglucose uptake by positron emission tomography (18FDG PET) to assess metabolic tissue activity, we measured decreased 18FDG uptake in most brain regions and marginally increased uptake in skeletal muscle of wildtype mice following stress. By contrast, 18FDG uptake did not change in brain and decreased in striated muscle in the mdx mouse model of DMD in response to stress, suggesting dysfunctional glucose-insulin signalling. Glucose intolerance in mdx mice was exacerbated by stress and driven not by an insensitivity to insulin, but by an inability to synthesize insulin. Exogenous administration of naked insulin mitigated immediate stress-induced physical inactivity (indirect measure of stress sensitivity), lowered 18FDG uptake in brain and elevated 18FDG uptake in striated muscle of mdx mice in response to stress. These data indicate that during stress, dystrophin-deficiency impairs the ability of brain and striated muscle to respond metabolically appropriately. It also suggests that the hypersensitive stress phenotype of mdx mice is associated with dysfunctional glucose-insulin signalling that can be mitigated with exogenous insulin. [ABSTRACT FROM AUTHOR]