Abstract:

Objective: The protective effects of thyroid hormone T3 on the dysfunction of pancreas in alloxan (ALX)-induced
diabetic mice were investigated in this study. Methods: Twenty-four Kunming mice were randomly divided into four groups,
including negative control group, ALX group, ALX plus T3 (ALX + T3) group, and T3 group, which were subjected to
intraperitoneal administration of normal saline, ALX, ALX plus T3, and T3, respectively. The levels of reactive oxygen
species (ROS) in blood were tested at 1, 4, 6, 12, and 24 h after injection. Blood glucose was tested every 3 days. Mice were
sacrificed at 28 days after injection. Whole pancreas and plasma were utilized for morphological and biochemical analyses.
The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), the contents of reduced
and oxidative glutathione (GSH and GSSG), the expression levels of antioxidant enzyme genes including Nrf2, SOD,
GSH-Px, and CAT, and the expression levels of the apoptosis-associated genes Caspase-3, Caspase-9, Bax, Bcl-2 were
examined in each group. Results: ALX induced a high level of blood glucose and ROS (P < 0.01), low level of insulin in plasma
(P < 0.01), and lower activities of antioxidant enzymes in plasma and pancreas (P < 0.01), as well as down-regulation of the
antioxidant enzyme genes and apoptosis-related genes (P < 0.01). T3 could ameliorate the enhancement of blood glucose and
defective insulin secretion. The redox imbalance caused by ALX, including the decrease of antioxidant enzyme activities and
gene expression levels, was counteracted by T3. Moreover, the up-regulated pro-apoptosis genes (Caspase-3, Caspase-9 and
Bax) and down-regulated anti-apoptosis Bcl-2 gene were counteracted by T3 remarkably (P < 0.01). Conclusion: T3 could
improve the redox status of ALX-induced diabetic mice and protect pancreatic β-cells from cell death to maintain normal
physiological function of pancreas.

Key words: thyroid hormone T3, alloxan, diabetes, pancreas