Title: Emergent Multicellular dynamics of the endocrine pancreas.
Most biological systems exist as multi-cellular structures, which consist of heterogeneous cell populations that show wide-ranging interactions over a defined architecture. The function of the overall system is therefore determined by the system architecture, properties of the constituent cells and the modes by which they interact. Understanding how such systems function and how dysfunction in disease ultimately arises is therefore complex. The islets of Langerhans located in the pancreas are critical for regulating glucose homeostasis via secretion of hormones such as insulin or glucagon. Failure of insulin secretion is the cause of most forms of diabetes. Beta cells within the islet form an electrically coupled network, whose activity is critical for appropriate glucose-regulated insulin secretion. There is substantial heterogeneity among the beta cells of the islet, including variations in cellular excitability, electrical coupling, insulin secretion and susceptibility to death and dysfunction. We will present our work that combines optical imaging, optogenetics and computer modeling approaches to discern how different populations of beta cells exert disproportionate control over the islet electrical activity. This includes discovering and characterizing sub-populations that control the islet glucose response, oscillatory dynamics and wave propagation. We will further present how these emergent characteristics are disrupted in the progression of diabetes and how they differ in the human islet. Such understanding will provide a more complete picture of the islet to inform regenerative medicine approaches to cure diabetes as well as to discover new targets for therapeutic treatments.