Quercetin, a Lead Compound against Type 2 Diabetes Ameliorates Glucose Uptake via AMPK Pathway in Skeletal Muscle Cell Line

Abstract

Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential. In addition, quercetin triggered a rise in intracellular calcium suggesting that calcium-calmodulin mediated protein kinase (CaMKK) may also be involved. Quercetin shared a similar mechanism with the well-known drug metformin, highlighting it as a promising compound for the management of type 2 diabetes. The AMPK signaling pathway could contribute to correction of insulin resistance through bypassing the insulin-regulated system for GLUT4 translocation.

Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases

“…Similar to resveratrol, other flavonoids and the biguanide metformin that is recommended as the first-line intervention for diabetes treatment and prevention, quercetin can activate the insulin-independent 5 adenosine monophosphate-activated protein kinase (AMPK) pathway of skeletal muscle cells, slowing the oxygen consumption of adenosine diphosphate in isolated mitochondria [59]. Also, quercetin can enhance the uptake of glucose in skeletal myocytes through an AMPK-dependent up-regulation of glucose transporter GLUT-4, which may occur independently of the insulin signaling under oxidative stress conditions [60]. In addition to this, several in vitro studies have confirmed that flavonoids may possess strong inhibitory activities on the intestinal α-glucosidase enzyme that catalyzes the cleavage of glucose from disaccharides, thereby delaying the absorption of glucose and flattening postprandial hyperinsulinemic/hyperglycemic excursions [61,62].…”

Preparation and Characterization of Quercetin‐Loaded Zein Nanoparticles by Electrospraying and Study of In Vitro Bioavailability

“…The chemical structure of quercetin consists of 15 carbon atoms with two aromatic rings connected by three-carbon bridges and three hydroxyl groups (−OH) in the position 3, 5, and 7 in hydroxychromen structure (rings A and C) and two in the position 3 and 4 in hydroxyphenyl structure (ring B; Lin & Zhou, 2018). At the biological level, health benefits have been attributed to quercetin (Kumar, Vijayalakshmi, & Nadanasabapathi, 2017), mainly to reduce the prevalence of chronic degenerative diseases such as cardiovascular diseases (Porcu et al, 2018;Terao, 2017), cancer (Granato et al, 2017;Wu et al, 2018), diabetes (Dhanya, Arya, Nisha, & Jayamurthy, 2017;Peng et al, 2017), and obesity (Nabavi, Russo, Daglia, & Nabavi, 2015;Ting et al, 2017).…”

Antidiabetic potential of Musa spp. inflorescence: a systematic review

“…In the research by Arun et al ., the cellular model was L6 myoblasts. These L6 skeletal muscle cells have been extensively used in recent investigations of phytochemical compounds with antidiabetic effects . This study used rosiglitazone (100 n m ) as a positive control and the entire inflorescence for the extractions.…”

“…These L6 skeletal muscle cells have been extensively used in recent investigations of phytochemical compounds with antidiabetic effects. [72,73] This study used rosiglitazone (100 nM) as a positive control and the entire inflorescence for the extractions. The L6 cells differentiated were pretreated with 50 and 100 lg/ ml methanol extract for 24 h, and were then washed with buffer and incubated with 2-NBDG (0.1 mM) for 30 min.…”