RETRACTED: Icariin Ameliorates Palmitate-Induced Insulin Resistance Through Reducing Thioredoxin-Interacting Protein (TXNIP) and Suppressing ER Stress in C2C12 Myotubes

Abstract

Both thioredoxin-interacting protein (TXNIP) and endoplasmic reticulum (ER) stress are implicated in skeletal muscle insulin resistance. Icariin has been found to mimic insulin action in normal skeletal muscle C2C12 cells and display anti-diabetic properties in diet-induced obese mice. However, the underlying molecular mechanism remains to be well-established. Herein, we tested the hypothesis that the protective effects of icariin on free fatty acid-induced insulin resistance were attributed to its regulation on TXNIP protein levels and ER stress in skeletal muscle cells. We found that TXNIP mediated the saturated fatty acid palmitate (PA)-induced insulin resistance in C2C12 myotubes. Icariin treatment significantly restored PA-reduced proteasome activity resulting in reduction of TXNIP protein and suppression of ER stress, as well as improvement of insulin sensitivity. Proteasome inhibition by its specific inhibitor MG132 obviously abolished the inhibitory effect of icariin on PA-induced insulin resistance. In addition, MG132 supplementation markedly abrogated the impacts of icariin on ER stress and TXNIP-mediated downstream events such as inflammation and STAT3 phosphorylation. These results clearly indicate that icariin improves PA-induced skeletal muscle insulin resistance through a proteasome-dependent mechanism, by which icariin downregulats TXNIP levels and inhibits ER stress.

Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

“…Inflammation and apoptosis are associated with the progress of OA, and anti-inflammatory agents could prevent OA development [18][19][20][21]. ICA, the extract of Epimedium, is known to have anti-oxidative, anti-neuroinflammatory, and anti-apoptotic effects and considered to be effective for a range of disorders, such as neoplasm, Alzheimer's disease, cerebral ischemia, depression, diabetes, and Parkinson's disease (PD) [22][23][24][25]. For OA, ICA was identified as an anti-osteoporotic and anti-inflammatory compound through multi-target mechanisms, including the suppression of NF-κB signaling and inhibition of MMP1, MMP3, and MMP13 expression or OPG-RANKL-RANK system via MAPK pathways [13][14][15].…”

Icariin Attenuates Amyloid-β (Aβ)-Induced Neuronal Insulin Resistance Through PTEN Downregulation

“…RT-qPCR was performed as described previously (Li et al, 2018). The primer sequences used were as follows: PTEN forward, 5′-GTCACTGCTTGTTGTTTGC-3′ and reverse, 5′-TTCTTTGTT GATAGCCTCCAC-3′; U6 forward, 5′-GCTTCGGCAGCAC ATATACTAAAAT-3′ and reverse, 5′-CGCTTCACGAATTT GCGTGTCAT-3′.…”

“…The chymotrypsin-like activity of the 20S proteasome in the cells was measured as described previously (Zhang et al, 2015;Li et al, 2018). Briefly, the cells were lysed with cytosolic extraction buffer (50 mM HEPES, pH 7.5, 20 mM KCl, 5 mM MgCl 2 , 2 mM ATP, 1 mM DTT, 0.025% Digitonin).…”

“…Quantification of proteins or phosphorylated proteins was performed by western blotting, as described previously (Zhang et al, 2015;Li et al, 2018). Briefly, the cells were lysed in lysis buffer (50 mM HEPES, pH 7.6, 150 mM NaCl, 1% Triton X-100, 10 mM NaF, 20 mM sodium pyrophosphate, 20 mM b-glycerol phosphate, 1 mM sodium orthovanadate, 10 mg/ml leupeptin, 10 mg/ml aprotinin, and 1 mM phenylmethanesulfonyl fluoride).…”

“…Icariin, a major bioactive component extracted from plants of the Epimedium genus (Liu et al, 2006), has been shown to ameliorate insulin resistance in skeletal muscle cells (Han et al, 2015;Li et al, 2018;Liu et al, 2019) and restore impaired hypothalamic insulin signaling in the rats with chronic unpredictable mild stress (Pan et al, 2013). Currently, icariin has been found to evoke the neuroprotective effects in vivo.…”