Thyroid hormone treatment decreases hepatic glucose production and renal reabsorption of glucose in alloxan-induced diabetic Wistar rats

Abstract

The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan‐induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Adult Male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 μg/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

Beneficial effects of thyroid hormone on adipose inflammation and insulin sensitivity of obese Wistar rats

“…Moreover, body weight gain was decreased in these animals, in agreement with a recent study, which demonstrated that T3 treatment reduces the adiposity and increased the lean mass of obese mice (da Silva Teixeira et al. ).…”

“…; Teixeira et al. ). It is relevant to stress that this dose of T3 treatment did not change the hemodynamic parameters in comparison to the control group.…”

“…The dose of T3 used herein was chosen because the physiological dose (0.3 lg/100 g BW) was unable to significantly improve insulin sensitivity and reduce inflammatory cytokine expression (data not shown). In addition, the T3 dose used in this study has been employed in previous studies Teixeira et al 2016). It is relevant to stress that this dose of T3 treatment did not change the hemodynamic parameters in comparison to the control group.…”

“…We have recently detected morphological and molecular alterations, characteristic of primary hypothyroidism, in the thyroid gland of alloxan-induced diabetic rats ). Furthermore, we have shown that triiodothyronine (T3) treatment has positive effects on insulin sensitivity in diabetic rats associated with a reduction in inflammatory cytokine expression, decreased hepatic glucose production and increased urinary glucose excretion Teixeira et al 2016).…”

Reduced blood glucose through thyroid hormone degradation product

“…This is in agreement with work on Wistar rats with diabetes induced by alloxan treated with T3 (Teixeira et al . ). These rats had reduced glucose production in conjunction with the reduced expression of GLUT2.…”