Fructose consumption is responsible for the onset of
insulin resistance (IR), and
metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by
glucose. The need of the hour is to identify
fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of
insulin resistance using HepG2 cells cultured in either
fructose or
glucose-rich environment is investigated. Human
hepatocellular carcinoma cells (HepG2) were grown under standard conditions in either-DMEM without
glucose (NC), DMEM with high
glucose 25 mM (Glu), DMEM-glucose+0.55 mM
fructose (FC1), DMEM-glucose+1 mM
fructose (FC2) or DMEM-glucose+1 mM fructose+0.1 µM
insulin (FC3). The cells were treated with either AM,
rutin,
quercetin,
metformin or
pioglitazone and assessed for levels of
hexokinase,
phosphofructokinase (PFK),
aldehyde dehydrogenase,
phosphatidylinositol kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3), mitochondrial target of
rapamycin (mTOR),
hypoxia-induced factor (HIF-1α),
vascular endothelial growth factor (
VEGF) and tumour
necrosis factor (TNF-α). Summarily, when results from
fructose- and
glucose-rich environment were compared, then (1) IR was more pronounced in former; (2) AM performed better in former; (3)
metformin and
pioglitazone were equivocal in either; (4)
rutin and
quercetin showed deviant effects from AM; and lastly (5) effects of
rutin were closer to AM than
quercetin. We hypothesize that AM ameliorates
fructose-induced IR through a mechanism which is distinct from standard drugs and not shared by individual phytoconstituents in
toto.