Myricetin attenuates hyperinsulinemia-induced insulin resistance in skeletal muscle cells

Abstract

Previous studies have shown that hyperinsulinemia is not only a marker of insulin resistance, but also the causative factor of peripheral tissue insulin resistance. It also has been suggested that prolonged high-dose insulin treatment can mimic the effects of hyperinsulinemia and exacerbate insulin resistance in skeletal muscle cells. However, how to prevent or reverse insulin resistance induced by hyperinsulinemia remains largely unclear.In the past few decades, the use of myricetin as an antidiabetic agent has gained much attention, but little information is available regarding the effects of myricetin on glucose uptake and hyperinsulinemia-induced insulin resistance in skeletal muscle cells. The present study focuses on the effect of myricetin on insulin signaling in skeletal muscle cell line C2C12 myotubes. Initially, the effect of myricetin under normal condition was determined. We found that myricetin's enhancement in glucose uptake coincided with both protein kinase B (Akt) and AMPactivated protein kinase (AMPK) activities. After that, the role of hyperinsulinemia was investigated. It was showed that prolonged high-dose insulin treatment inhibited both Akt and AMPK activities. As the results, the low-dose insulin stimulation of glucose uptake was inhibited by hyperinsulinemia. However, the treatment of myricetin improved low-dose insulin-stimulated glucose uptake in the hyperinsulinemic state, and this effect essentially depended on the AMPK signal pathway. Together, our data suggest a putative link between hyperinsulinemia and insulin resistance in C2C12 myotubes, and the myricetin treatment stimulates glucose uptake and attenuates insulin resistance.

Mechanism of Action of Nutraceuticals on Intestine to Ameliorate Glucose Homeostasis: Follow-up Studies by an In Situ Approach

“…From our results, myricitrin seems to be a powerful inhibitor of SGLT1 activity and also has alternative sites of action in intestine. Interestingly, these results are additive with antidiabetic effect of myricitrin by acting on aldose reductase and on glucose uptake in C2C12 myotubules under normal and insulin-stimulated conditions [33], suggesting a relevant role of myricitrin on glycemia homeostasis. In our experimental conditions using 10mM of glucose, phlorizin effectively blocked the glucose absorption indicating that SGLT1 is inhibited.…”

Modulation of Glucose Transporter Protein by Dietary Flavonoids in Type 2 Diabetes Mellitus

“…Berberine has also been reported to be responsible for moderate inhibition of mitochondrial function, decreased oxygen consumption and enhanced glycolysis which lead to increased AMP/ATP ratio and subsequent activation of AMPK pathway 81 , 154 , 156 . In a study conducted by Ding and his group 157 , myricetin intervention revealed the attenuation for the inhibitory effect of hyperinsulinemia on glucose uptake through increasing AMP-activated protein kinase activity in C2C12 myotubes.…”

Role of red grape polyphenols as antidiabetic agents

“…During a drug screening study among 30 bioflavonoids on glucose uptake under normal and insulin-stimulated conditions in C2C12 myotubes, it was found that myricetin was the only compound that stimulated insulin-mediated lipogenesis 52 . The insulin-mimicking effect of myricetin has also been reported on glucose transport in adipocytes of rats with noninsulin-dependent diabetes 53 …”

“…An array of health-promoting effects of myricetin has been demonstrated 50, 51. Apart from myricetin's antioxidative, antiviral, and anticarcinogenic activities, consumption of myricetin and reduced risk of diabetes have been reported in many studies 51, 52…”

“…Myricetin is used as a traditional medicine in northern Brazil to control hyperglycemia 52 . Studies performed on diabetic rats revealed that myricetin prevents the condition of hyperglycemia through different mechanisms.…”