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Chronic treatment with the thiazolidinedione, MCC‐555, is associated with reductions in nitric oxide synthase activity and β‐cell apoptosis in the pancreas of the Zucker Diabetic Fatty rat
Author(s) -
Pickavance Lucy C.,
Widdowson Peter S.,
Foster John R.,
Williams Gareth,
Wilding John P. H.
Publication year - 2003
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1046/j.1365-2613.2003.00337.x
Subject(s) - medicine , endocrinology , thiazolidinedione , nitric oxide , nitric oxide synthase , diabetes mellitus , apoptosis , pancreas , insulin , islet , pancreatic islets , type 2 diabetes , chemistry , biochemistry
Summary. The Zucker Diabetic Fatty (ZDF) rat is a model of impaired insulin sensitivity arising from hyperphagia owing to a mutation in the leptin receptor. In time, young ZDF rats, which are not initially diabetic, develop impaired pancreatic β‐cell function leading to apoptotic cell death. This results in an inability to fully compensate for the reduction in insulin sensitivity with hypersecretion of insulin. Young, pre‐diabetic ZDF rats were treated, over a 4‐week period, with the thiazolidinedione compound MCC‐555, and the islet morphology studied in comparison to ZDF rats not given MCC‐555. In particular, changes in the apoptotic incidence, as measured using TUNEL staining to localize apoptotic cells, were studied over the 4‐week period. Changes in the induction of nitric oxide synthase and in the accumulation of nitrate/nitrite within the pancreas were also studied during the time course of administration of MCC‐555. The study has demonstrated that the administration of MCC‐555 significantly decreases the apoptotic incidence in the islets of Langerhans of pre‐diabetic ZDF rats given the compound, as compared to those not given MCC‐555, as well as decreasing the accumulation of nitrate/nitrite within the pancreas.