Signaleringsnätverk för frisättning av Langerhanska ö-hormoner

This project aims to clarify how pancreatic islet hormone secretion is regulated in health and disease with focus on insulin, glucagon and somatostatin release from β-, α-, and δ-cells.

Islet hormone release is controlled by nutrients, neurohormonal and paracrine factors, but there are major gaps in the understanding of how the regulatory effects are mediated by various messengers and signalling proteins and how defects in the signalling processes lead to aberrant secretion of the hormones in both type 2 and type 1 diabetes.

Advanced live-cell fluorescence imaging, optogenetics and secretion assays will be used to elucidate the subcellular dynamics of intracellular messenger concentrations (ATP, Ca2+, cAMP, signalling lipids), localization and activity of signalling proteins (kinases, small GTPases and their regulators), as well as secretory activity and paracrine interactions between the islet cells during nutrient and neurohormonal stimulation.

Signalling and secretion will also be investigated in islets from diabetic donors and in experimental models of diabetes.

A better comprehension of the signalling networks underlying islet hormone secretion provides a basis for understanding disease pathogenesis and for identifying new mechanisms that can be targeted to improve glucose control in diabetes patients.