Proposed by: Dr. Caroline Arous, Dept. of Cell Physiology and Metabolism, University of Geneva.

Type 2 Diabetes (T2D) is characterized by the death of insulin-producing pancreatic β-cells, which affects insulin secretion, leading to an impairment of glucose homeostasis. β-cells are localized within the islet of Langerhans inside the pancreatic tissue. In addition to the β-cells, pancreatic islets contain also a network or scaffold of fibrous or sheet like extracellular structures, also called extracellular matrix (ECM) to which β-cells are attached, and which supports their secretory function, in so far non-understood ways. In T2D, this ECM scaffold is modified or reduced and could therefore be involved or responsible for β-cell dysfunctions. β-cells are linked to the ECM via cell-surface receptors called β1-integrins. These receptors can regulate many cellular functions such as survival and insulin secretion in β-cells, but it is not known whether their function is affected by high glucose levels found in diabetic individuals. The goal of our project is to determine how different types of ECM affect β1-integrin-mediated secretion of insulin and β-cell survival, and to study how the context of T2D is impairing the function of the β1-integrin receptor. Our preliminary results propose that β1-integrin activity is affected by high glucose concentration (for example during hyperglycemia), resulting in reduced cell survival, but also in a change in the deposition and organization of the ECM scaffold. By understanding the glucose-mediated effect, we hope to provide new information how the tissue architecture and β-cell function is affected in T2D and how the function of the β1-integrin receptor can be improved.