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γ-谷氨酰转移酶处理对 2 型糖尿病大鼠模型中 JNK1 基因表达和蛋白活化的影响。

Effect of gamma conglutin treatment on JNK1 gene expression and protein activation in a rat model of type 2 diabetes.

机构信息

Instituto de Investigación en Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.

Departamento de Botánica y Zoología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, México.

出版信息

Pharm Biol. 2021 Dec;59(1):374-380. doi: 10.1080/13880209.2021.1893757.

Abstract

CONTEXT

Gamma conglutin (Cγ) from lupine species represents a potential complementary treatment for type 2 diabetes mellitus (T2DM) because of its hypoglycaemic effect. However, its underlying mechanism of action is not fully known.

OBJECTIVE

To evaluate whether Cγ from M. E. Jones (Fabaceae) modulates c-Jun N-terminal kinase 1 (JNK1) expression and activation in a T2DM rat model.

MATERIALS AND METHODS

Gamma conglutin isolated from seeds was characterized by SDS-PAGE. Fifteen Wistar rats with streptozotocin-induced T2DM (HG) were randomized into three groups ( = 5): vehicle administration (HG-Ctrl), oral treatment with Cγ (120 mg/kg/day) (HG-Lr) for one week, and treatment with metformin (300 mg/kg/day) (HG-Met); a healthy group (Ctrl,  = 5) was included as control. The levels of glucose and biomarkers of renal and hepatic function were measured pre- and post-treatment. Hepatic expression and phosphorylation of JNK1 were evaluated by qRT-PCR and western blot, respectively.

RESULTS

Oral treatment with either Cγ or metformin reduced serum glucose level to 86.30 and 74.80 mg/dL, respectively ( ˂ 0.05), from the basal levels. expression was 0.65- and 0.54-fold lower ( ˂ 0.05) in the HG-Lr and HG-Met groups, respectively, than in HG-Ctrl. Treatment with Cγ decreased JNK1 phosphorylation. However, Cγ did not change the levels of kidney and liver biomarkers.

DISCUSSION AND CONCLUSIONS

Treatment with Cγ from inhibited expression, , suggesting JNK1 as a potential therapeutic target in diabetes and revealing one mechanism underlying the hypoglycaemic effect of lupine Cγ. Nevertheless, further studies are required.

摘要

背景

羽扇豆属(Fabaceae)的γ-球蛋白(Cγ)因其降血糖作用,有望成为 2 型糖尿病(T2DM)的一种补充治疗方法。然而,其作用机制尚不完全清楚。

目的

评估 M. E. Jones 羽扇豆属 Cγ 是否调节 2 型糖尿病大鼠模型中的 c-Jun N 端激酶 1(JNK1)表达和激活。

材料和方法

通过 SDS-PAGE 对从种子中分离出的 Cγ进行表征。将 15 只链脲佐菌素诱导的 2 型糖尿病(HG)Wistar 大鼠随机分为三组(每组 5 只): vehicle 组(HG-Ctrl)、Cγ(120mg/kg/天)口服治疗组(HG-Lr)1 周、二甲双胍(300mg/kg/天)治疗组(HG-Met);同时纳入 5 只健康对照组(Ctrl)。治疗前后测量血糖和肝肾功能生物标志物水平。采用 qRT-PCR 和 Western blot 分别评估肝 JNK1 的表达和磷酸化。

结果

与基础水平相比,Cγ或二甲双胍口服治疗分别将血清葡萄糖水平降低至 86.30 和 74.80mg/dL( ˂ 0.05)。HG-Lr 和 HG-Met 组的 表达分别降低了 0.65-和 0.54 倍( ˂ 0.05)。Cγ 处理降低了 JNK1 磷酸化。然而,Cγ 并未改变肾脏和肝脏生物标志物的水平。

讨论与结论

来自羽扇豆属的 Cγ 治疗抑制了 表达,表明 JNK1 可能是糖尿病的一个潜在治疗靶点,揭示了羽扇豆 Cγ 降血糖作用的一种机制。然而,还需要进一步的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c5/8018548/fb2ce32e81ae/IPHB_A_1893757_F0001_B.jpg

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