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维生素D通过调节Akt、磷酸烯醇式丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)的表达来提高有氧运动训练的抗糖尿病效果。

Vitamin D improves the antidiabetic effectiveness of aerobic training via modulation of Akt, PEPCK, and G6Pase expression.

作者信息

Hoseini Zahra, Behpour Nasser, Hoseini Rastegar

机构信息

Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, P.O. Box. 6714967346, Kermanshah, Iran.

出版信息

Diabetol Metab Syndr. 2023 Sep 9;15(1):184. doi: 10.1186/s13098-023-01158-y.

DOI:10.1186/s13098-023-01158-y
PMID:37689713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10492382/
Abstract

BACKGROUND

Although the effect of Vitamin D Supplementation (Vit D) on several chronic diseases has been well conceded, its role in diabetes remains ambiguous. The present study investigated the interactive effects of Aerobic Training (AT) and different Vit D doses on Protein Kinase B (Akt), Phosphoenolpyruvate Carboxylase (PEPCK), and Glucose-6-Phosphatase (G6Pase) protein expressions in hepatocytes of type-2 diabetic rats.

METHODS

Fifty-six male Wistar rats were divided into 2 groups SHAM (non-diabetic control; n = 8), and diabetic (n = 48). Then, diabetic rats were divided into six groups: AT with high doses of Vit D (D + AT + HD), AT with moderate doses of Vit D (D + AT + MD), high doses of Vit D (D + HD), moderate doses of Vit D (D + MD), AT receiving vehicle (sesame oil; D + AT + oil), and control (oil-receiving). D + AT + HD and D + HD groups received 10,000 IU of Vit D; while D + AT + MD and D + MD groups receive 5000 IU of Vit D once a week by injection; D + AT + oil and SHAM groups received sesame oil. Diabetes was induced via intraperitoneal (IP) injection of streptozotocin (50 mg/kg body weight). After 2 months of intervention, serum insulin, glucose, and visceral fat were measured; protein expressions of Akt, PEPCK, and G6Pase were assessed by western blotting. The paired t-test, one-way analysis of variance (One-Way ANOVA), and the Tukey post hoc test were used at the signification level of P < 0.05.

RESULTS

Our data indicate that the diabeticization of rats increased the level of insulin, glucose, and PEPCK and G6Pase protein expressions and decreased the expression of the Akt (P < 0.05 for all variables). Combined AT and moderate or high Vit D significantly reduced body weight (P = 0.001; P = 0.001), body mass index (P = 0.001; P = 0.002), food intake (P = 0.001; P = 0.001) comparing the pre-test with the post-test, respectively. Also, AT and either high or moderate Vit D alone therapies lead to the improvement of the metabolic state, however, their combination had a more significant effect on the treatment of type 2 diabetes.

CONCLUSIONS

Findings from the present study suggested that combined Vit D supplementation and AT successfully improve liver function and attenuate insulin resistance via upregulating Akt and downregulating PEPCK and G6Pase expressions, compared with monotherapy.

摘要

背景

尽管补充维生素D(Vit D)对多种慢性疾病的影响已得到充分认可,但其在糖尿病中的作用仍不明确。本研究探讨了有氧运动训练(AT)和不同剂量的Vit D对2型糖尿病大鼠肝细胞中蛋白激酶B(Akt)、磷酸烯醇丙酮酸羧化酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)蛋白表达的交互作用。

方法

56只雄性Wistar大鼠分为2组,假手术组(非糖尿病对照组;n = 8)和糖尿病组(n = 48)。然后,将糖尿病大鼠分为6组:高剂量Vit D联合有氧运动训练组(D + AT + HD)、中剂量Vit D联合有氧运动训练组(D + AT + MD)、高剂量Vit D组(D + HD)、中剂量Vit D组(D + MD)、接受载体(芝麻油)的有氧运动训练组(D + AT + oil)和对照组(接受油)。D + AT + HD组和D + HD组接受10000 IU的Vit D;而D + AT + MD组和D + MD组每周通过注射接受5000 IU的Vit D;D + AT + oil组和假手术组接受芝麻油。通过腹腔注射链脲佐菌素(50 mg/kg体重)诱导糖尿病。干预2个月后,测量血清胰岛素、血糖和内脏脂肪;通过蛋白质印迹法评估Akt、PEPCK和G6Pase的蛋白表达。采用配对t检验、单因素方差分析(One-Way ANOVA)和Tukey事后检验,显著性水平为P < 0.05。

结果

我们的数据表明,大鼠糖尿病化增加了胰岛素、血糖水平以及PEPCK和G6Pase蛋白表达,并降低了Akt的表达(所有变量P < 0.05)。与测试前相比,AT联合中或高剂量Vit D显著降低了体重(P = 0.001;P = 0.001)、体重指数(P = 0.001;P = 0.002)、食物摄入量(P = 0.001;P = 0.001)。此外,单独的AT和高或中剂量Vit D疗法均可改善代谢状态,然而,它们的联合对2型糖尿病的治疗效果更显著。

结论

本研究结果表明,与单一疗法相比,补充Vit D与AT联合可通过上调Akt并下调PEPCK和G6Pase表达,成功改善肝功能并减轻胰岛素抵抗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/ea00b0fd41b5/13098_2023_1158_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/2228ac9995e1/13098_2023_1158_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/61d287fcdf73/13098_2023_1158_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/ea00b0fd41b5/13098_2023_1158_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/2228ac9995e1/13098_2023_1158_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/61d287fcdf73/13098_2023_1158_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/4b1cea6d111a/13098_2023_1158_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eae/10492382/ea00b0fd41b5/13098_2023_1158_Fig4_HTML.jpg

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