Thymoquinone Preserves Pancreatic Islets Structure Through Upregulation of Pancreatic beta-Catenin in Hypothyroid Rats

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Diabetes Metab Syndr Obes. 2021 Jun 29;14:2913-2924. doi: 10.2147/DMSO.S317417. eCollection 2021.

ABSTRACT

BACKGROUND: Altered status of thyroid hormones, which have a key role in regulating metabolism, was reported to affect glucose homeostasis and insulin secretion.

OBJECTIVE: This study was designed to assess the impact of propylthiouracil (PTU)-induced hypothyroidism on the pancreatic islet cells and the efficacy of thymoquinone (TQ) in alleviating this impact and explore the mechanism behind it alleviating oxidative stress and affecting β-catenin expression.

MATERIALS AND METHODS: PTU (6 mg/kg/body weight) was used to induce hypothyroidism in Wistar rats. Four groups of rats (n=6 each) were utilized in this study. Untreated hypothyroid and TQ-treated hypothyroid groups (50 mg/kg/body weight for 4 weeks) were included. Thyroid functions, antioxidant profile and pancreatic β-catenin and IL-10 mRNA were measured. Histopathological and immunohistochemical assessment of the pancreas was performed.

RESULTS: PTU administration induced a hypothyroid status that was associated with a marked disturbed oxidant/antioxidant status and a significant hyperglycemia (p<0:001), hypoinsulinemia (p=0.01) and decreased HOMA-β-cell (p<0.001). Islet cells of hypothyroid pancreas showed many degenerative changes with increased apoptosis, reduced insulin β-catenin immunoexpression. Administration of TQ alleviated these effects on the thyroid function, antioxidants, structure of pancreatic islet cells. Up-regulation of β-catenin, IL-10 and CAT gene expression in pancreatic islets after treatment with TQ supported its antioxidant and preserving β-cell function and viability mechanistic action.

CONCLUSION: TQ alleviated PTU-induced hypothyroidism changes in insulin homeostasis and pancreatic β cells mostly through its antioxidant effect as well as up-regulation of pancreatic β-catenin expression.

PMID:34234489 | PMC:PMC8254558 | DOI:10.2147/DMSO.S317417