Altered Spatial Metabolism in Diabetes

Profound cell signaling alterations are known to occur in altered metabolic states such as type 1 diabetes (T1D). In the pancreas, the sequence of events involved in glucose-stimulated insulin secretion can be disrupted at many different molecular points along its biological pathway. Most tissue-based imaging modalities used to date have focused on genetic or protein signatures of T1D dysfunction. However, it is the metabolites that are directly interacting with and modulating the collective “-omic” levels, including gene expression, RNA metabolism, protein activity, and metabolic activity. Additionally, the metabolome is increasingly recognized as a more dynamic and sensitive measure of an organism’s phenotype. In contrast to classical antibody-based fluorescence imaging modalities, imaging mass spectrometry is a label-free imaging technology that allows for the multiplexed and facile discrimination of hundreds of individual metabolites. Detecting the endocrine/exocrine partitioning and diversity of metabolites directly in pancreatic tissue, before these metabolites have been diluted in the bloodstream, promises an unprecedented view of T1D metabolism.