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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% CO 2  and then preincubated with Gelam honey extracts (20, 40, 60, and 80  µ g/mL) as well as quercetin (20, 40, 60, and 80  µ M), 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-  κ  B, 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-  κ  B, 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-  κ  B, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly.  Conclusion . Gelam honey-induced differential expression of MAPK, NF-  κ  B, 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.

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