Journal
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 60, Issue 10, Pages 749-760Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1369/0022155412457048
Keywords
extracellular matrix; hyaluronan; islet; proteoglycan
Categories
Funding
- Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care System (Seattle, WA), National Institutes of Health [DK088082, DK017047]
- Juvenile Diabetes Research Foundation [nPOD 25-2010-648]
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The pancreatic islet comprises endocrine, vascular, and neuronal cells. Signaling among these cell types is critical for islet function. The extracellular matrix (ECM) is a key regulator of cell-cell signals, and while some islet ECM components have been identified, much remains unknown regarding its composition. We investigated whether hyaluronan, a common ECM component that may mediate inflammatory events, and molecules that bind hyaluronan such as versican, tumor necrosis factor-stimulated gene 6 (TSG-6), and components of inter-a-trypsin inhibitor (I alpha I), heavy chains 1 and 2 (ITIH1/ITIH2), and bikunin, are normally produced in the pancreatic islet. Mouse pancreata and isolated islets were obtained for microscopy (with both paraformaldehyde and Carnoy's fixation) and mRNA. Hyaluronan was present predominantly in the peri-islet ECM, and hyaluronan synthase isoforms 1 and 3 were also expressed in islets. Versican was produced in alpha cells; TSG-6 in alpha and beta cells; bikunin in alpha, beta, and delta cells; and ITIH1/ITIH2 predominantly in beta cells. Our findings demonstrate that hyaluronan, versican, TSG-6, and IaI are normal islet components and that different islet endocrine cell types contribute these ECM components. Thus, dysfunction of either alpha or beta cells likely alters islet ECM composition and could thereby further disrupt islet function. (J Histochem Cytochem 60:749-760, 2012)
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