This connection seen between growth hormones and insulin may be a biochemical feedback loop in which lack of GHR leads to hyperinsulinemia and subsequent upregulation of GHR in the liver and expression of IGF-1 [93,94], leading to the hypothesis that a metabolic condition inducing hyperinsulinemia may be a source of increased activity of growth hormone and subsequent IGF-1 action leading to cell proliferation in the body. Here, INS is linked to hyperinsulinism.