Type 1 diabetes (T1D) is a devastating multifactorial disorder manifested by the autoimmune destruction of insulin-producing beta cells leading to insulin deficiency. Our overarching aim is to investigate the spaciochemical changes in the human exocrine and endocrine pancreata during various stages of T1D with unmatched chemical specificity and multiplexity. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) will be used for multiplexed direct measurement of metabolites, lipids and peptides in control, no diabetes autoantibody positive and affected by clinically diagnosed T1D pancreata sections. Two groups of T1D affected donors will be investigated as well as no diabetes autoantibody positive group and compared to control group and group developed T2D. Donors will be similar to ones described in 1. The first will be those with less than one year since disorder diagnosis and the second with more than 7 years since diagnosis. C-peptide levels have to drop approximately 10 times for each group with most advanced T1D cases exhibiting lowest concentrations. We will perform a comparative analysis of the pancreas head and pancreas body regions which demonstrate different extent of damage during T1D progression.1 Also, for comparative analysis of malfunctioning pancreas biochemistry, we are requesting sections of late stage T2D-affected pancreata. This work will provide direct information on the multiplexed chemical heterogeneity and plasticity in the exocrine and endocrine tissues of the pancreatic head and body in health and disorder. This effort involves new and innovative measurement technologies including ones developed in collaboration with the nPOD2 to obtain information on metabolite, lipid, and peptides. Including their spatial distributions; these data cannot be easily obtained by other methods. This research will improve our understanding of the changes of tissue surrounding beta cell destruction in T1D by elucidating the chemical signals characteristic of T1D in comparison with control and T2D, and may help to identify novel factors and pathways for therapeutic intervention to treat this disease.
