Hyaluronan: A Mediator of Islet Dysfunction and Destruction in Diabetes?

J Histochem Cytochem. 2015 Aug;63(8):592-603. doi: 10.1369/0022155415576542.

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.

Keywords: diabetes; extracellular matrix; hyaladherins; hyaluronan; islet.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Humans
  • Hyaluronic Acid / metabolism*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology

Substances

  • Hyaluronic Acid