Vaccinium ashei leaves extract alleviates insulin resistance via AMPK independent pathway in C2C12 myotube model

Abstract

Blueberry (Vaccinium ashei) leaf has recently attracted attention as an anti-obesity food component. In this study, we examined the effects of blueberry leaf extract (BLEx) on insulin signaling in C2C12 differentiated myoblasts. The results showed that BLEx promotes the intracellular uptake of 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]−2-deoxy-D-glucose (2-NBDG) and phosphorylation of Akt under insulin stimulation. In addition, pretreatment with BLEx ameliorated TNF-α-nduced insulin resistance with regard to 2-NBDG uptake and Akt phosphorylation. Moreover, BLEx prevented the TNF-α−induced activation of JNK and NF-kB pathways and phosphorylation of IRS-1 at serine residue. BLEx failed to induce phosphorylation of AMPK as well as did not prevent the restoration of 2-NBDG uptake under TNF-α–induced insulin resistance. Overall, skeletal muscle is a putative target for the anti-diabetic effect of BLEx by amelioration of insulin resistance.

C2C12 cell model: its role in understanding of insulin resistance at the molecular level and pharmaceutical development at the preclinical stage

“…The increase in glucose utilisation was linked to AMPK activation (insulin-independent signalling pathway) [202] Vaccinium ashei leaf…”

“…[203] As blueberry could alleviate the impairment of insulin transduction that was associated to TNF-a treatment, it would be a promising antidiabetic agent to restore glucose uptake. [202] The application of C2C12 cells in pharmaceutical development of drug delivery systems…”

“…[ 201 ] One of the studies investigated the effect of blueberry leaf extract on insulin signalling cascade and glucose metabolism in C2C12 differentiated myoblasts. [ 202 ] The findings revealed that blueberry leaf extract could induce glucose uptake irrespective of insulin stimulation. TNF‐α is one of the adipokines that can activate JNK signalling pathway and phosphorylating serine site of IRS‐1.…”

A milk casein hydrolysate‐derived peptide enhances glucose uptake through the AMP‐activated protein kinase signalling pathway in skeletal muscle cells

“…Moreover, long‐term metformin treatment appears to enhance insulin‐stimulated glucose uptake in an AMPK‐dependent manner (Kristensen et al., 2014). In addition, several foods such as cinnamon extract (Shen et al., 2014), blueberry leaf (Yamasaki et al., 2018), resveratrol (Park et al., 2007) and xanthene derivatives (Kwon et al., 2014) enhance glucose uptake through AMPK activation. Therefore, activating AMPK in skeletal muscles may aid in the treatment and prevention of metabolic diseases and improve physical performance.…”

A Multicomponent Intervention Program With Overweight and Obese Adolescents Improves Body Composition and Cardiorespiratory Fitness, but Not Insulin Biomarkers

“…The increase in body fat accelerates the process of chronic inflammation of adipose tissue, causing hormonal dysfunction and leading to a high release of inflammatory cytokines (Galic et al, 2010 ). Several cytokines expressed in obesity can manipulate the action of the insulin hormone (Wensveen et al, 2015 ), such as resistin, which inhibits the signaling of its receptors (Yamasaki et al, 2018 ) and increases lipolysis in cells of fat, causing a greater release of fatty acids (Nakamura et al, 2014 ). As a consequence, high levels of free fatty acids can cause insulin resistance in tissues, such as liver and muscles (Zhang et al, 2011 ), a worrying fact considering that insulin resistance is known as the first phase for the development of cardiometabolic diseases (Patel et al, 2013 ).…”