Loss of insulin secretion is a recognised characteristic of type 2 diabetes. It is therefore an important goal to determine how insulin secretion is controlled and what goes wrong in disease.
We have recently shown that insulin secretion in pancreatic beta cells is targeted towards the vasculature and that synaptic scaffold proteins, such as liprin, are present in beta cells and enriched at the vascular face of the cells . The molecular mechanisms that might orientate the beta cell with respect to the vasculature are unknown and here we test the hypothesis that cell polarity is important.
Immunofluorescent staining of fixed pancreatic slices was used to determine the location of known determinants of cell polarity, such as Par3, Dlg and Scribble. Apical determinants, such as Par3 are enriched on the beta cell membrane opposite to the vasculature. In contrast, basal determinants, such as Scribble, are located on the lateral and vascular face of beta cells.
To mechanistically test the idea that cell polarity is important in secretion we use dispersed beta cells cultured on glass or in Matrigel. Our results show that the different culture conditions do alter the positioning of the determinants of polarity. We also show that the location of liprin, a protein associated with targeting of secretion, is altered when cell polarity is changed. In ongoing work we are investigating the location of other proteins associated with secretory control and are developing methods to directly measure any changes in targeting of insulin secretion. We are also using heterozygous Scribble knockout mice (Scrib+/- mice)  to dissect out the pathways of control.
We conclude beta cells are polarised and have a consistent orientation with respect to the vasculature. Our current data imply that polarity may be important in insulin secretion in beta cells.