Why is human insulin secretion temporally disrupted in diabetes?

Diabetes is a life-threatening disease caused by abnormalities in insulin production. The yearly cost to the NHS of diabetes is forecast at £39.8Bn by 2035. The condition is characterised by defects in insulin secretion from pancreatic islets: Type 1 diabetes is characterised by absolute insulin deficiency and Type 2 diabetes by insufficient insulin secretion. Islets are balls of ~1500 cells that function optimally in 3-D and commonly used biological tests that use cells grown on glass do not represent well the situation in the body. Our team has developed sophisticated microscopy, using the more ‘traditional’ biology in cultured cells, that can reveal enormous detail about insulin secretion inside single living cells. Working with SNBTS and clinical endocrinologists in our collaborative team, we have the opportunity to rapidly translate these assays into relevant 3-D islets – not using animals, but jumping ahead to human donor islets. We will combine our unique imaging, of healthy and diabetic islets, with the best current biochemical analyses by working with Miltenyi Biotec, to generate new, much needed, insight into the cellular defects that underlie diabetes in humans. This work will reveal directly unknown pathways that we suspect from circumstantial evidence are disrupted in disease formation.