• Journal of Ginseng Research
• /
• v.48 no.1
• /
• pp.12-19
• /
• 2024

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

• Journal of Life Science
• /
• v.17 no.1 s.81
• /
• pp.56-63
• /
• 2007

Insulin stimulates the fusion of intracellular vesicles containing glucose transporter 4 (GLUT4) with plasma membrane in adipocytes and muscle cells. Here we show that adipocyte differentiation results in enhanced insulin sensitivity of glucose uptake. On the other hand, glucose uptake in response to platelet-derived growth factor (PDGF) stimulation was markedly reduced by adipocyte differentiation. Expression level of insulin receptor and caveolin-1 was dramatically increased during adipocyte differentiation. Adipocyte differentiation caused :ilightly enhanced activation of acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) by insulin stimulation. However, activation of Akt by PDGF stimulation was largely reduced. Activation of ERK was not detected in both fibroblasts and adipocytes after stimulation with insulin. PDGF-dependent activation of ERK was reduced by adipocyte differentiation. Insulin-dependent glucose uptake was abrogated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, in both fibroblasts and adipocytes. Also disassembly of caveolae structure by $methyl-\beta-cyclodextrin$ caused impairment of Akt activation and glucose uptake. Finally, insulin receptor, Akt, SH2-domain-containing inositol 5-phosphatase 2 (SHIP2), and regulatory subunit of PI3K are localized at lipid raft domain and the translocation was facilitated upon insulin stimulation. Given these results, we suggest that lipid raft provide proper site for insulin action for glucose uptake.

• Journal of Life Science
• /
• v.33 no.11
• /
• pp.859-867
• /
• 2023

Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.