Pancreatic exocrine-endocrine crosstalk in diabetes development

Common for most diabetes variants are deregulated secretion from the β-cells within the pancreatic islet of Langerhans. In recent years we focused our work to understand defect islet hormone secretion in Type-2 diabetes (T2D) and Cystic Fibrosis Related Diabetes (CFRD). We have discovered novel microRNA (miRNAs) involved in the post-transcriptional regulation of gene expression essential for insulin secretion in the β-cells. Interestingly, miRNAs can act as signalling molecules in the crosstalk between different tissues during disease development. In addition, we have preliminary data indicating that other peptides, TGF-β and IGFBP7, have key roles in the crosstalk between exocrine and endocrine pancreas.
We hypothesize that knowledge of the islet and blood-based miRNA profile can be utilized in development of novel therapeutics and in prediction of T2D and CFRD. We further postulate that blood-based miRNAs, TGF-β and IGFBP7 are involved in the crosstalk between exocrine pancreas and the insulin secreting β-cells and thereby influence β-cell function and disease development.
Therefore, we aim to 1) Examine blood-based microRNAs in cardiometabolic disease and CFRD; 2) Investigate exocrine-endocrine crosstalk during development of diabetes; and 3) Decipher human islet miRNA networks to disclose central miRNAs in diabetes development to be used in development of novel treatment of disease.
We expect the suggested project to reveal new methods in diabetes therapeutics and diagnostics.