This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The pulsatile release of insulin is achieved through coordinated activity of hundreds of b-cells within the islet. This periodic release is important for the efficiency of most of the organs targeted by insulin. A lack of coordination in the activity of insulin secreting b-cells, and the other cells present in the islet, will affect the periodicity of insulin release and consequently the activity of the target organs. The periodic pattern of insulin secretion is altered in type-2 diabetes patients. Considerable work has been undertaken on the mechanisms of insulin secretion from the single beta cell. Less attention is paid to the coordination of activity within the islets and between the islets. The overall purpose of the study undertaken in this sub-project is to perfect approaches to address the mechanisms of intra and inter islet coordination. Currently, we are pursuing a series of experiments and technology developments designed to assess the overall hypothesis that regulated insulin secretion, from primary, reconstituted or ductal cell derived islets, depends on the intra-islet organization, inclusive of coordinated cell function, cell-cell communication and the balance of heterogeneous cell types. We address this hypothesis by combining new and established procedures for generating islets with novel and established experimental procedures to monitor the islet metabolic state, insulin secretion and cellular connectivity within the islets.
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