Inhibition of Microsomal Triglyceride Transfer Protein Expression and Apolipoprotein B100 Secretion by the Citrus Flavonoid Naringenin and by Insulin Involves Activation of the Mitogen-Activated Protein Kinase Pathway in Hepatocytes

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FIG. 6.
FIG. 6.

Proposed signaling pathways for naringenin- and insulin-mediated increases in LDL-r expression, decreases in MTP expression, and inhibition of apoB100 secretion in HepG2 cells. Naringenin and insulin increase (A) PI 3-kinase activity and (B) ERK1/2 phosphorylation via MEK1/2 activation. Naringenin activates both pathways independent of IRS-1/2 phosphorylation (pY). Naringenin may bypass the insulin receptor by activating the GTPase Ras. Naringenin and insulin activate MAPKp38, which attenuates MEK1/2 activity; however, MEK1/2 activation predominates, resulting in increased ERK1/2 phosphorylation.

This Article

  1. Diabetes vol. 54 no. 6 1676-1683