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lüll Identification of a novel mechanism regulating beta-cell mass: neuronal relay from the liver to pancreatic beta-cells Imai J; Oka Y; Katagiri HIslets 2009[Jul]; 1 (1): 75-7Recent studies have demonstrated that beta-cell replication plays a central role in maintaining adult beta-cell mass. beta-cell proliferative activity changes dynamically to meet systemic needs throughout life. One condition in which beta-cell proliferation is enhanced is obesity-related insulin resistance. However, the mechanism underlying this compensatory beta-cell response is not well understood. We have identified a neuronal relay, originating in the liver, which enhances both insulin secretion and pancreatic beta-cell proliferation. Blockade of this neural relay in murine obesity models inhibited pancreatic islet expansion during obesity development, showing this inter-organ communication system to be physiologically involved in compensatory beta-cell proliferation. While there is controversy about which mechanism, proliferation of pre-existing beta-cells or production of new beta cells from progenitor cells, plays the dominant role in maintaining or regulating beta-cell mass, we herein provide an example that proliferation of pre-existing beta-cells contributes to a beta-cell increment in obesity-related insulin resistance. Furthermore, we have shown the potential for clinical application of this inter-organ system as a therapeutic target for insulin-deficient diabetes.|Adult[MESH]|Animals[MESH]|Cell Count[MESH]|Humans[MESH]|Insulin-Secreting Cells/*cytology/physiology[MESH]|Islets of Langerhans/*anatomy & histology/*innervation[MESH]|Liver/*innervation/physiology[MESH]|Models, Biological[MESH]|Neural Pathways/*physiology[MESH]|Organ Size[MESH] |