12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets

If you need an accessible version of this item, please submit a remediation request.
Date
2017-08-01
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Oxford University Press
Abstract

Context:

The 12-lipoxygenase (12-LO) pathway produces proinflammatory metabolites, and its activation is implicated in islet inflammation associated with type 1 and type 2 diabetes (T2D). Objectives:

We aimed to test the efficacy of ML355, a highly selective, small molecule inhibitor of 12-LO, for the preservation of islet function. Design:

Human islets from nondiabetic donors were incubated with a mixture of tumor necrosis factor α , interluekin-1β, and interferon-γ to model islet inflammation. Cytokine-treated islets and human islets from T2D donors were incubated in the presence and absence of ML355. Setting:

In vitro study. Participants:

Human islets from organ donors aged >20 years of both sexes and any race were used. T2D status was defined from either medical history or most recent hemoglobin A1c value >6.5%. Intervention:

Glucose stimulation. Main Outcome Measures:

Static and dynamic insulin secretion and oxygen consumption rate (OCR). Results:

ML355 prevented the reduction of insulin secretion and OCR in cytokine-treated human islets and improved both parameters in human islets from T2D donors. Conclusions:

ML355 was efficacious in improving human islet function after cytokine treatment and in T2D islets in vitro. The study suggests that the blockade of the 12-LO pathway may serve as a target for both form of diabetes and provides the basis for further study of this small molecule inhibitor in vivo.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Ma, K., Xiao, A., Park, S. H., Glenn, L., Jackson, L., Barot, T., … Nadler, J. L. (2017). 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets. The Journal of clinical endocrinology and metabolism, 102(8), 2789–2797. doi:10.1210/jc.2017-00267
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
The Journal of Clinical Endocrinology and Metabolism
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
This item is under embargo {{howLong}}