Journal article
Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes
The journal of clinical endocrinology and metabolism, Vol.100(3), pp.E387-E395
03/01/2015
DOI: 10.1210/jc.2014-3630
PMCID: PMC4333045
PMID: 25532042
Abstract
Context: Inflammation in the pancreas can cause β-cell stress, leading to diabetes development. Access to human pancreas tissues via the Network for Pancreatic Organ Donors with Diabetes (nPOD) has allowed characterization of pathways leading to this inflammation. Objective: 12-Lipoxygenase (12-LO) induces inflammation and has been implicated in diabetes development. Our goal was to determine expression of 12-LO in human islets from control, autoantibody-positive, type 1 diabetic, and type 2 diabetic nPOD pancreas donors. Design: Pancreas tissues from nPOD donors were examined by immunohistochemistry and immunofluorescence for islet expression of 12-LO in different subsets of islet cells. Participants: Donor pancreas samples were obtained from nPOD based on disease status (control, n = 7; autoantibody-positive, n = 8; type 1 diabetic, n = 17; or type 2 diabetic donors, n = 15). Main Outcome Measure: Determination of 12-LO expression within human islets served as the main outcome measure, including distinguishing which types of islet cells expressed 12-LO. Results: Islets from control participants (nondiabetic) lacked islet expression of 12-LO. Of donors in the other groups, 25% to 37% expressed islet 12-LO with a clear inverse relation between the numbers of β-cells and 12-LO+ cells within islets of 12-LO+ cases. 12-LO expression was not seen within macrophages, endothelial cells, α-cells, or β-cells, but only within cells expressing low levels of pancreatic polypeptide (PP) and increased levels of vimentin. Conclusions: 12-LO expression colocalizes within a specific type of islet PP+ cell under prediabetic and diabetic conditions. The costaining of PP and vimentin suggests that 12-LO participates in the process leading to β-cell dedifferentiation in the islet.
Details
- Title: Subtitle
- Expression Pattern of 12-Lipoxygenase in Human Islets With Type 1 Diabetes and Type 2 Diabetes
- Creators
- Wojciech J Grzesik - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Norfolk, Virginia 23507Joseph L Nadler - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Norfolk, Virginia 23507Yui Machida - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Norfolk, Virginia 23507Jerry L Nadler - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Norfolk, Virginia 23507Yumi Imai - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Norfolk, Virginia 23507Margaret A Morris - Strelitz Diabetes Center, and Department of Microbiology and Molecular Cell Biology (M.A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23507
- Resource Type
- Journal article
- Publication Details
- The journal of clinical endocrinology and metabolism, Vol.100(3), pp.E387-E395
- DOI
- 10.1210/jc.2014-3630
- PMID
- 25532042
- PMCID
- PMC4333045
- ISSN
- 0021-972X
- eISSN
- 1945-7197
- Language
- English
- Date published
- 03/01/2015
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094377602771
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