Table 2. Changes in protein expression between metformin- and insulin-treated cells.

proteins (12) with differential expression compared to untreated controls (|log2FC| ≥ 0.5) that were regulated by metformin and hyperinsulinemia in the same way
upregulated:	CD69, FCER2
downregulated:	COL1A1, EGFR, FLOT1, IL1B, IL2, IL15, IRS2, KDR, RP9, S100B
proteins (8) with significantly differential expression compared to untreated controls (|log2FC| ≥ 0.5 and p ≤ 0.05) that were significantly higher expressed after metformin treatment compared to hyperinsulinemia
CTSL, F3, GUSB, LGALS1, LGMN, NT5E, PI3, PLAUR
proteins (24) with significantly differential expression compared to untreated controls (|log2FC| ≥ 0.5 and p ≤ 0.05) that were significantly higher expressed during hyperinsulinemia compared to metformin treatment
AMFR, CCND2, CD63, CDCP1, CDH5, CEACAM8, EGF, ERBB3, ETS2, EZR, GDF15, GPX4, IRF4, MPP3, PLCG2, SELE, SIGLEC5, SORL1, SPP1, THBS1, TM9SF2, VEGFA, VTCN1, WNT2B
proteins (8) without differential expression compared to untreated controls (|log2FC| < 0.5), but with significantly differential expression between metformin treatment and hyperinsulinemia
ERBB3, ETS2, GDF15, GPX4, LGALS1, LGMN, NT5E, THBS1

A total of 44 proteins were differentially expressed between metformin and insulin-treated groups, of which only 12 proteins were regulated in the same way. The remaining 32 proteins were regulated in different ways by metformin and insulin, of which 8 proteins were significantly higher expressed after metformin administration, whereas 24 proteins were significantly more prominent during hyperinsulinemia. A total of 8 proteins were differentially expressed between both treatments groups without notable changes compared to the respective untreated control samples.