title: Hyaluronan: A Mediator of Islet Dysfunction and Destruction in Diabetes?
abstract: Hyaluronan (HA) is an extracellular matrix (ECM) component that is present in mouse and human islet ECM. HA is localized in peri-islet and intra-islet regions adjacent to microvessels. HA normally exists in a high molecular weight form, which is anti-inflammatory. However, under inflammatory conditions, HA is degraded into fragments that are proinflammatory. HA accumulates in islets of human subjects with recent onset type 1 diabetes (T1D), and is associated with myeloid and lymphocytic islet infiltration, suggesting a possible role for HA in insulitis. A similar accumulation of HA, in amount and location, occurs in non-obese diabetic (NOD) and DORmO mouse models of T1D. Furthermore, HA accumulates in follicular germinal centers and in T-cell areas in lymph nodes and spleen in both human and mouse models of T1D, as compared with control tissues. Whether HA accumulates in islets in type 2 diabetes (T2D) or models thereof has not been previously described. Here we show evidence that HA accumulates in a mouse model of islet amyloid deposition, a well-known component of islet pathology in T2D. In summary, islet HA accumulation is a feature of both T1D and a model of T2D, and may represent a novel inflammatory mediator of islet pathology.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington (RLH)
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
authors.affiliation: Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington (MB, NN, PYJ, TNW)
authors.forename: Marika
authors.initials: M
authors.lastname: Bogdani
authors.affiliation: Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington (MB, NN, PYJ, TNW)
authors.forename: Nadine
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington (MB, NN, PYJ, TNW)
authors.forename: Pamela Y
authors.initials: PY
authors.lastname: Johnson
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington (TNW)
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology
chemical_list: D006820:Hyaluronic Acid
keywords: diabetes; extracellular matrix; hyaladherins; hyaluronan; islet