Structure Function Relationships in the Pancreatic Islet of Langerhans

Dillon Jevon, University of Sydney, Australia

 

Aims

Efforts to differentiate β cells from stem cells will be improved if a better understanding of the intact islet environment’s effect on insulin secretion is gained. Pancreatic Islets of Langerhans are most commonly isolated from enzymatic digestions which removes intra-islet capillaries and alters β cell structure. However, pancreatic islets are highly vascularised and β cells form domains with respect to capillaries. Recent advances in organotypic pancreatic slicing have allowed live cell imaging of structurally intact islets in which I have observed the quantity of insulin exocytosis being dependent on the contact β cells make with capillaries. Furthermore, focal adhesion kinase (FAK) is activated specifically at β cell domains contacting capillaries and inhibiting FAK activation reduces glucose stimulated insulin secretion. This project aims to translate these findings to cell culture. Will larger capillary contact area in vitro lead to increased glucose stimulated insulin secretion and is the observed increase FAK dependent?

Aim 1
Culture β cells on glass coverslips which have been covalently bound with the capillary extracellular matrix protein, laminin, to determine if different surface areas of contact alters their glucose induced insulin secretion.

Aim 2
Determine whether FAK knockout abolishes the correlation of capillary area contact to insulin secretion.

 

Grant awarded: £3,024.00