Effect of Gelam Honey on the Oxidative Stress-Induced Signaling Pathways in Pancreatic Hamster Cells

Abstract

Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β-cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF-κB, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF-κB, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance.

Peer Review #1 of "Honey reduces the metastatic characteristics of prostate cancer cell lines by promoting a loss of adhesion (v0.1)"

“…shown that honey can reduce the expression and nuclear translocation of NF-κB both in vivo and in vitro (Batumalaie et al, 2013;Hussein et al, 2013), although honeys were also shown not to inhibit NF-κB activity in glioblastoma cells U87MG (Moskwa et al, 2014). However, Moskwa et al did show that honeys could reduce enzymatic activity of MMP-2 and MMP-9 (Moskwa et al, 2014).…”

Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

“…In obesity, an increased efflux of FFAs from adipocytes leads to activation of pro-inflammatory signaling pathways via ROS. Increased oxidative stress is associated with stimulation of IKKβ and activation of transcription factor NF-κB which in turn mediates an inflammatory response by increasing expression of several pro-inflammatory cytokines including TNF-α, IL1-β, IL6 and MCP-1 19 20 21 . In the present study, PA induced IKKβ and NF-κB p65 phosphorylation resulted in higher level of TNF-α and IL-6 generation in endothelial cells.…”

“…The activated PI3-K then stimulates downstream Akt and eNOS, which initiates NO production 30 . Inflammatory cytokines such as TNF-α, IL-6 and IKKβ activation can increase serine phosphorylation of IRS-1, with subsequent reduction in insulin-dependent tyrosine phosphorylation of IRS-1 thereby impairing PI3K/Akt/eNOS pathway of insulin signaling 19 20 . The present study demonstrated that PA blocked the phosphorylation of IRS-tyrosine by inducing IRS-1 serine phosphorylation in HUVECs in response to insulin.…”

Insulin Resistance Provides the Connection Between Hepatitis C Virus and Diabetes

“…HCV promotes dysfunction of insulin signaling pathways via several distinct mechanisms. One of our recent studies on HIT-T15 cells, cultured under hyperglycemic conditions demonstrated increased insulin resistance with a significant increase in the levels of MAPK, NF-κB and IRS-1 serine phosphorylation (ser307) and decreased Akt and insulin contents ( 10 ). Similarly, studies demonstrated that HCV infection also induces insulin resistance through impairment of IRS-1 and AKT, in particular, increasing the IRS-1 phosphorylation at serine residues and decreasing it at tyrosine residues ( 11 , 12 ).…”