In contrast, PTEN, stimulated by TNF-alpha, promotes apoptosis through its actions on NF-KB.[14,15] In addition to decreasing circulating insulin levels through increased insulin receptor sensitivity, metformin has been shown to decrease IGF-1 receptor and insulin receptor expression in endometrial cancer cell lines.[16] The lower levels of circulating insulin and IGF-1 reduce the amount of binding to the insulin receptor, especially to isoform A in cancer cells, leading to less tumor growth.[17]. Here, INS is linked to cancer.