INS and neoplasm: Furthermore, when serum insulin levels, tumor IR expression and Akt phosphorylation were grouped as a summary variable and patients were assessed individually, those exhibiting the largest reductions in insulin, tumor IR and p-Akt exhibited the largest reductions in tumor cell proliferation (Additional file 8) (r = 0.41, P = 0.012), supporting a role for the insulin-dependent effects of metformin in its mechanism of antitumor action.