González-Santiago Ana E, Vargas-Guerrero Belinda, García-López Pedro M, Martínez-Ayala Alma L, Domínguez-Rosales José A, Gurrola-Díaz Carmen M
Instituto de Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y Genómica, C.U.C.S, Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia C.P, 44350, Guadalajara, Jalisco, México.
Departamento de Botánica y Zoología, C.U.C.B.A, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Plant Foods Hum Nutr. 2017 Jun;72(2):134-140. doi: 10.1007/s11130-016-0597-7.
Lupinus albus seeds contain conglutin gamma (Cγ) protein, which exerts a hypoglycemic effect and positively modifies proteins involved in glucose homeostasis. Cγ could potentially be used to manage patients with impaired glucose metabolism, but there remains a need to evaluate its effects on hepatic glucose production. The present study aimed to analyze G6pc, Fbp1, and Pck1 gene expressions in two experimental animal models of impaired glucose metabolism. We also evaluated hepatic and renal tissue integrity following Cγ treatment. To generate an insulin resistance model, male Wistar rats were provided 30% sucrose solution ad libitum for 20 weeks. To generate a type 2 diabetes model (STZ), five-day-old rats were intraperitoneally injected with streptozotocin (150 mg/kg). Each animal model was randomized into three subgroups that received the following oral treatments daily for one week: 0.9% w/v NaCl (vehicle; IR-Ctrl and STZ-Ctrl); metformin 300 mg/kg (IR-Met and STZ-Met); and Cγ 150 mg/kg (IR-Cγ and STZ-Cγ). Biochemical parameters were assessed pre- and post-treatment using colorimetric or enzymatic methods. We also performed histological analysis of hepatic and renal tissue. G6pc, Fbp1, and Pck1 gene expressions were quantified using real-time PCR. No histological changes were observed in any group. Post-treatment G6pc gene expression was decreased in the IR-Cγ and STZ-Cγ groups. Post-treatment Fbp1 and Pck1 gene expressions were reduced in the IR-Cγ group but increased in STZ-Cγ animals. Overall, these findings suggest that Cγ is involved in reducing hepatic glucose production, mainly through G6pc inhibition in impaired glucose metabolism disorders.
白羽扇豆种子含有凝集素γ（Cγ）蛋白，该蛋白具有降血糖作用，并能正向调节参与葡萄糖稳态的蛋白质。Cγ可能可用于治疗葡萄糖代谢受损的患者，但仍需要评估其对肝脏葡萄糖生成的影响。本研究旨在分析两种葡萄糖代谢受损实验动物模型中葡萄糖-6-磷酸酶（G6pc）、果糖-1,6-二磷酸酶1（Fbp1）和磷酸烯醇式丙酮酸羧激酶1（Pck1）基因的表达。我们还评估了Cγ治疗后肝脏和肾脏组织的完整性。为建立胰岛素抵抗模型，雄性Wistar大鼠自由饮用30%蔗糖溶液，持续20周。为建立2型糖尿病模型（链脲佐菌素模型），对5日龄大鼠腹腔注射链脲佐菌素（150 mg/kg）。每个动物模型随机分为三个亚组，每天接受以下口服治疗，持续一周：0.9% w/v氯化钠（赋形剂；胰岛素抵抗对照组和链脲佐菌素对照组）；二甲双胍300 mg/kg（胰岛素抵抗二甲双胍组和链脲佐菌素二甲双胍组）；以及Cγ 150 mg/kg（胰岛素抵抗Cγ组和链脲佐菌素Cγ组）。治疗前后使用比色法或酶法评估生化参数。我们还对肝脏和肾脏组织进行了组织学分析。使用实时聚合酶链反应定量G6pc、Fbp1和Pck1基因的表达。任何组均未观察到组织学变化。治疗后，胰岛素抵抗Cγ组和链脲佐菌素Cγ组的G6pc基因表达降低。治疗后，胰岛素抵抗Cγ组的Fbp1和Pck1基因表达降低，但链脲佐菌素Cγ组动物的表达增加。总体而言，这些发现表明，Cγ主要通过抑制葡萄糖代谢受损疾病中的G6pc参与降低肝脏葡萄糖生成。
