12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets.
J Clin Endocrinol Metab
; 102(8): 2789-2797, 2017 08 01.
Article
en En
| MEDLINE
| ID: mdl-28609824
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-1ß, 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 OutcomeMeasures:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Consumo de Oxígeno
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Sulfonamidas
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Islotes Pancreáticos
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Inhibidores de la Lipooxigenasa
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Diabetes Mellitus Tipo 2
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Glucosa
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Insulina
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2017
Tipo del documento:
Article