Mata-Torres Gerardo, Andrade-Cetto Adolfo, Espinoza-Hernández Fernanda Artemisa, Cárdenas-Vázquez René
Laboratorio de Etnofarmacología, Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Laboratorio de Biología Animal Experimental, Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Pharmacol. 2020 Mar 3;11:215. doi: 10.3389/fphar.2020.00215. eCollection 2020.
hepatic glucose production or hepatic gluconeogenesis is the main contributor to hyperglycemia in the fasting state in patients with type 2 diabetes (T2D) owing to insulin resistance, which leads to at least twice as much glucose synthesis compared to healthy subjects. Therefore, control of this pathway is a promising target to avoid the chronic complications associated with elevated glucose levels. Patients with T2D in the rural communities of Mexico use medicinal plants prepared as infusions that are consumed over the day between meals, thus following this rationale (consumption of the infusions in the fasting state), one approach to understanding the possible mechanism of action of medicinal plants is to assess their capacity to inhibit hepatic glucose production. Furthermore, in several of these plants, the presence of phenolic acids able to block the enzyme glucose-6-phosphatase (G6Pase) is reported. In the present work, extracts of , , , , and , which are Mexican plants that have been traditionally used to treat T2D, were assayed to evaluate their possible hepatic glucose output (HGO) inhibitory activity with a pyruvate tolerance test in 18-h fasted STZ-NA Wistar rats after oral administration of the extracts. In addition, the effects of the extracts on the last HGO rate-limiting enzyme G6Pase was analyzed. Our results showed that four of these plants had an effect on hepatic glucose production in the or assays. and extracts decreased glucose output, preventing an increase in the blood glucose levels and sustaining this prevented increase after pyruvate administration. Moreover, both extracts inhibited the catalytic activity of the G6Pase complex. On the other hand, even though and did not exhibit a significant effect, had the most potent inhibitory effect on this enzymatic system, while the extract only inhibited hepatic glucose production in the pyruvate tolerance test. Because of the traditional method in which diabetic patients use plants, hepatic glucose production inhibition seems to be a mechanism that partially explains the common hypoglycemic effect. However, further studies must be carried out to characterize other mechanisms whereby these plants can decrease HGO.
由于胰岛素抵抗,肝糖生成或肝糖异生是2型糖尿病(T2D)患者空腹状态下高血糖的主要原因,与健康受试者相比,这会导致至少两倍的葡萄糖合成。因此,控制这一途径是避免与血糖水平升高相关的慢性并发症的一个有前景的靶点。墨西哥农村社区的T2D患者使用制成浸剂的药用植物,在两餐之间全天饮用,因此基于这一原理(在空腹状态下饮用浸剂),了解药用植物可能作用机制的一种方法是评估它们抑制肝糖生成的能力。此外,据报道,在其中几种植物中存在能够阻断葡萄糖-6-磷酸酶(G6Pase)的酚酸。在本研究中,对墨西哥传统上用于治疗T2D的、、、和的提取物进行了测定,通过丙酮酸耐量试验评估其对18小时禁食的链脲佐菌素-烟酰胺(STZ-NA)Wistar大鼠口服提取物后可能的肝糖输出(HGO)抑制活性。此外,分析了提取物对最后一个HGO限速酶G6Pase的影响。我们的结果表明,其中四种植物在或试验中对肝糖生成有影响。和提取物降低了葡萄糖输出,防止血糖水平升高,并在给予丙酮酸后维持这种降低的状态。此外,两种提取物均抑制了G6Pase复合物的催化活性。另一方面,尽管和没有表现出显著影响,但对该酶系统具有最强的抑制作用,而提取物仅在丙酮酸耐量试验中抑制肝糖生成。由于糖尿病患者使用植物的传统方法,抑制肝糖生成似乎是部分解释常见降血糖作用的一种机制。然而,必须进行进一步的研究以阐明这些植物降低HGO的其他机制。