PMID- 25532042
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20181113
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 100
IP  - 3
DP  - 2015 Mar
TI  - Expression pattern of 12-lipoxygenase in human islets with type 1 diabetes and 
      type 2 diabetes.
PG  - E387-95
LID - 10.1210/jc.2014-3630 [doi]
AB  - CONTEXT: Inflammation in the pancreas can cause beta-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 beta-cells and 12-LO(+) cells within islets 
      of 12-LO(+) cases. 12-LO expression was not seen within macrophages, endothelial 
      cells, alpha-cells, or beta-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 beta-cell dedifferentiation in the 
      islet.
FAU - Grzesik, Wojciech J
AU  - Grzesik WJ
AD  - Department of Internal Medicine (W.J.G., J.L.N., Y.M., J.L.N., Y.I.), Strelitz 
      Diabetes Center, and Department of Microbiology and Molecular Cell Biology 
      (M.A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23507.
FAU - Nadler, Joseph L
AU  - Nadler JL
FAU - Machida, Yui
AU  - Machida Y
FAU - Nadler, Jerry L
AU  - Nadler JL
FAU - Imai, Yumi
AU  - Imai Y
FAU - Morris, Margaret A
AU  - Morris MA
LA  - eng
GR  - R01 DK090490/DK/NIDDK NIH HHS/United States
GR  - UC4 DK104166/DK/NIDDK NIH HHS/United States
GR  - 1 UC4 DK104166-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141222
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (Vimentin)
RN  - 59763-91-6 (Pancreatic Polypeptide)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
SB  - IM
MH  - Arachidonate 12-Lipoxygenase/*genetics/metabolism
MH  - Autoantibodies/metabolism
MH  - Cell Dedifferentiation/genetics
MH  - Diabetes Mellitus, Type 1/*genetics/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism/pathology
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Islets of Langerhans/*metabolism/pathology
MH  - Pancreas Transplantation
MH  - Pancreatic Polypeptide/metabolism
MH  - Tissue Donors
MH  - Vimentin/metabolism
PMC - PMC4333045
EDAT- 2014/12/23 06:00
MHDA- 2015/05/13 06:00
PMCR- 2016/03/01
CRDT- 2014/12/23 06:00
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 14-3630 [pii]
AID - 10.1210/jc.2014-3630 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2015 Mar;100(3):E387-95. doi: 10.1210/jc.2014-3630. Epub 
      2014 Dec 22.