Figure 9.

Atorvastatin inhibits insulin synthesis by inhibiting the Ras complex (Ras/Raf/extracellular signal-regulated kinase/CREB) in INS-1 cells. HMG-CoA reductase inhibitor inhibited Ras proteins by inhibiting the generation of farnesyl pyrophosphate ester, and reduced the phosphorylation of a series of downstream substrates, such as Raf-1 kinase, mitogen-activated protein kinase (MAPK) kinase, and MAPK, p90rsk. Inhibition of MAPK and p90rsk activation further inhibited the phosphorylation of nuclear transcription factor CREB and then influenced the binding quantity of CREB and cAMP response element, thereby inhibiting the activity of insulin promoter. CREB = cAMP response element-binding protein, HMG-COA = 3-hydroxy-3-methyl glutaryl coenzyme A.