Polyol accumulation in muscle and liver in a mouse model of type 2 diabetes

Aims: Type 2 diabetes (T2D) is a complex metabolic disease leading to complications in multiple organs. Diabetic myopathy and liver disease are common complications of T2D, but are incompletely understood. To gain insight into the pathogenesis of these conditions we performed metabolomic analysis of skeletal muscle and liver in a mouse model of T2D. Methods: Tissue metabolomics were performed by GC/MS and LC/MS of the skeletal muscle and liver in the MKR mouse model of T2D, compared with control mice. MKR mice were treated with the beta-3 adrenergic receptor agonist, CL-316,243 to determine metabolite changes after correcting hyperglycemia. Results: Blood glucose was higher in MKR vs WT mice, and normalized with CL-316,243 treatment. Compared with WT mice, MKR mice had 2.5 fold higher concentrations of sorbitol and 1.7 fold lower concentrations of reduced glutathione in skeletal muscle. In liver, MKR mice had 2 fold higher concentrations of the pentitol ribitol. CL-316,243 treatment normalized sorbitol and ribitol concentrations in MKR skeletal muscle and liver, respectively to the levels of the WT mice. Conclusions: These results demonstrate tissue-specific accumulation of polyols in a mouse model of T2D and provide novel insights into the pathogenesis of myopathy and liver disease in T2D. (C) 2016 Elsevier Inc. All rights reserved.