Abstract
Objective We aim to explore the effects and mechanisms of Jinlida granules on the dysfunction of hypothalamic-pituitary-thyroid (HPT) axis in diabetic rats induced by streptozotocin. Methods A total of 48 SD rats were randomized into normal control group (NC, n = 6) and diabetic group (n = 42). Rats in diabetic group were randomly divided into diabetes mellitus (DM) control group, low, medium, and high doses of Jinlida group (JL, JM, and JH), medium dose of Jinlida plus Tongxinluo group (JM + T), metformin group (Met), and Saxagliptin group (Sax) (n = 6 in each group). Diabetic rats were obtained by intraperitoneal injection of streptozotocin and sacrificed at 8 weeks to examine the function of HPT axis. Results Levels of fasting blood glucose (P < 0.05), pIκB, TNFα (P < 0.05), pNF-κB, and IL-6 (P < 0.01) in liver tissue and TSHR mRNA expression (P < 0.01) in diabetic group were significantly increased, while levels of serum T3 and T4, thyroid hormone receptor (TR) mRNA and Dio1 mRNA in liver tissue, and sodium iodide symporter (NIS) mRNA in thyroid tissue in diabetic group were significantly decreased compared with those in NC group (P < 0.01). Among diabetic groups, level of fasting blood glucose in JH, JM + T and Met group was lower (P < 0.05) compared with DM group. However, levels of serum T3 and T4, TR mRNA in liver tissue, TSHR, and NIS mRNA in thyroid tissue in JH, JM + T, Met, and Sax group were significantly increased (P < 0.01) compared to DM group. In contrast, levels of Dio1 mRNA, pI-κB in Met and JM + T groups, pNF-κB in JH, JM + T, and Met group, and TNFα and IL-6 in JM, JH, JM + T, and Met group were significantly decreased (P < 0.05). HE staining showed reduced thyroid follicular epithelium and follicular area, as well as increased colloid area in DM group, indicating impaired synthesis, reabsorption, and secretory of TH in diabetes, which was significantly improved in JH, JM + T, and Met groups. Conclusion HPT axis dysfunction in DM could be significantly improved by Jinlida granules. The mechanism might be associated with the anti-inflammatory effects involving NF-κB pathway. Our findings suggested the potential benefit of Jinlida granules for patients with HPT axis dysfunction and DM, which was to be verified by more experimental and clinical studies.
Highlights
Thyroid diseases and diabetes mellitus (DM) represent two most common endocrine disorders, both of which involve multiple organs
We aim to evaluate the effect of Jinlida granules on levels of hypothalamic-pituitary-thyroid (HPT) axis hormones, TH receptor, and thyroid stimulating hormone (TSH) receptor in diabetic rats induced by streptozotocin (STZ)
Results showed that the fasting blood glucose in diabetic group was higher than that in NC group (P < 0.05), which was significantly decreased in JH, JM + T, and metformin group (Met) group compared to DM group (P < 0.05) (Figure 1(b))
Summary
Thyroid diseases and diabetes mellitus (DM) represent two most common endocrine disorders, both of which involve multiple organs. The common predisposing genes are detected for DM and thyroid diseases by Genome-Wide Association Study [1]. Various clinical studies suggest a significantly increased incidence of thyroid dysfunction in patients with DM [2, 3], and one study indicates that the ratio of TT4, TT3, FT3, and TT3/rT3 in DM patients is significantly lower compared to normal group [4]. Thyroid dysfunction is closely related to insulin resistance [5]. Subclinical hypothyroidism has been reported to be associated with insulin resistance [10,11,12]. A meta-analysis shows that subclinical hypothyroidism is associated with an increased risk of diabetic peripheral neuropathy, diabetic peripheral arterial disease, diabetic nephropathy, and diabetic retinopathy in patients with T2DM [13]. Diabetes can cause thyroid dysfunction, which, in turn, exacerbates DM and its complications
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