The complexity of diabetes as a disease necessitates novel therapeutic and diagnostic avenues. An emerging trend in pharmacology is RNA-based therapeutics targeting non-coding RNA genes (ncRNA), i.e. genes which do not code for proteins but rather transcribe functional RNA molecules as the final gene product. However, the potential of using such approach in diabetes may not be fully realized until the roles of ncRNA genes in glucose homeostasis are reasonably elucidated. Recent studies have also shown the presence of stable RNAs circulating in the blood after tissue injuries. Because many transcripts are expressed in cell-type enriched manner, it should be possible to monitor the progress of specific cellular damage by measuring RNAs which has leaked into the bloodstream. In micro- and macro-vascular diabetic complications, cellular damage in affected tissues remains undetected until major pathophysiological symptoms are already manifested. This proposal has the following aims: i) establish the global ncRNA landscape in the pancreatic islets with RNA sequencing, ii) elucidate the roles of emerging ncRNA genes in glucagon and insulin secretion, and iii) investigate the potential of circulating RNAs as blood-based biomarkers in predicting the onset of diabetes, as well as monitoring the progression of its various complications. Identification of ncRNA genes important for glucose homoeostasis will bring additional arsenal in diabetes therapy, while early monitoring of the disease via blood-based RNA biomarkers will significantly improve personalised diabetes treatment.