Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Biomed Pharmacother. 2024 Aug;177:117053. doi: 10.1016/j.biopha.2024.117053. Epub 2024 Jun 29.
The main objective of this study was to find if thiamine disulfide (TD) lowers blood glucose level and improves insulin resistance (IR) in liver and muscle in rats with chronic type 1 diabetes (T1DM) using euglycemic-hyperinsulinemic clamp technique.
A total of fifty male Wistar rats were assigned to five groups consisted of: non-diabetic control (NDC), diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with both TD and insulin (D-insulin+TD). Diabetes was induced by a 60 mg/kg dose of streptozotocin. Blood glucose levels, pyruvate tolerance test (PTT), intraperitoneal glucose tolerance test (IPGTT), levels of glycosylated hemoglobin (HbA1c), glucose infusion rate (GIR), liver and serum lipid profiles, liver glycogen stores, liver enzymes ([ALT], [AST]), and serum calcium and magnesium levels. were evaluated. Additionally, gene expression levels of phosphoenolpyruvate carboxykinase (Pepck), forkhead box O1 (Foxo1), and glucose transporter type 4 (Glut4) were assessed in liver and skeletal muscle tissues.
Blood glucose level was reduced by TD treatment. In addition, TyG index, HOMA-IR, serum and liver lipid profiles, HbA1c levels, and expressions of Foxo1 and Pepck genes were decreased significantly (P<0.05) in all the treated groups. However, TD did not influence Glut4 gene expression, but GIR as a critical index of IR were 5.0±0.26, 0.29±0.002, 1.5±0.07, 0.9±0.1 and 1.3±0.1 mg.minKg in NDC, DC, D-TD, D-insulin and D-insulin+TD respectively.
TD improved IR in the liver primarily by suppressing gluconeogenic pathways, implying the potential use of TD as a therapeutic agent in diabetes.
本研究的主要目的是使用正葡萄糖-高胰岛素钳夹技术，观察二硫丁基（TD）是否能降低慢性 1 型糖尿病（T1DM）大鼠的血糖水平并改善其肝、肌肉胰岛素抵抗（IR）。
将 50 只雄性 Wistar 大鼠随机分为 5 组：非糖尿病对照组（NDC）、糖尿病对照组（DC）、糖尿病硫辛酸治疗组（D-TD）、糖尿病胰岛素治疗组（D-胰岛素）和糖尿病硫辛酸与胰岛素联合治疗组（D-胰岛素+TD）。糖尿病由 60mg/kg 链脲佐菌素诱导。评估血糖水平、丙酮酸耐量试验（PTT）、腹腔内葡萄糖耐量试验（IPGTT）、糖化血红蛋白（HbA1c）水平、葡萄糖输注率（GIR）、肝和血清脂质谱、肝糖原储存、肝酶（ALT、AST）和血清钙镁水平。此外，还评估了肝和骨骼肌组织中磷酸烯醇丙酮酸羧激酶（Pepck）、叉头框 O1（Foxo1）和葡萄糖转运蛋白 4（Glut4）的基因表达水平。
TD 治疗降低了血糖水平。此外，在所有治疗组中，TyG 指数、HOMA-IR、血清和肝脂质谱、HbA1c 水平以及 Foxo1 和 Pepck 基因的表达均显著降低（P<0.05）。然而，TD 不影响 Glut4 基因表达，但作为 IR 关键指标的 GIR 分别为 5.0±0.26、0.29±0.002、1.5±0.07、0.9±0.1 和 1.3±0.1mg.minKg，在 NDC、DC、D-TD、D-胰岛素和 D-胰岛素+TD 组中分别为。
TD 通过抑制糖异生途径改善了肝内 IR，表明 TD 作为糖尿病治疗药物具有潜在的应用价值。
