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. 2017 Mar 7;313(2):E148–E166. doi: 10.1152/ajpendo.00241.2016

Fig. 9.

Fig. 9.

Menin inhibitor increases transcript levels of GLP1R and proliferation marker Ki67 in human islets. A: menin inhibitor treatment (50, 200, and 500 nM) of human islets from donor 1 (50 yr old) for 48 h increases GLP1R mRNA levels compared with vehicle controls. Treatment of human islets for 7 days with either menin inhibitor alone (MI-2-2, 250 nM or 500 nM), exendin-4 alone (100 nM), or a combination of MI22 (500 nM) and exendin-4 (100 nM) increases GLP1R mRNA levels (B and D) and Ki67 mRNA levels (C and E) compared with vehicle (DMSO)-treated controls. F: schematic depicting proposed role of menin and PRMT5 in regulating GLP1 signaling: 1, Menin and PRMT5 downregulate GLP1R transcript; 2, GLP1R agonists and forskolin induce phosphorylation of FOXO1 via a PKA-mediated mechanism; 3, Menin suppresses GLP1R agonist and forskolin-induced and PKA-mediated phosphorylation of FOXO1 and CREB; 4, Menin increases both transcript and protein levels of FOXO1; 5, PRMT5 interacts with CREB and FOXO1, and symmetric dimethylation of conserved arginines surrounding the target serines blocks PKA-mediated phosphorylation of these serine residues.