In addition, some of our group have shown that β-cell specific deletion of the negative regulator of insulin signaling PTEN (phosphatase and tensin homolog), which dephosphorylates PIP3 to phosphatidylinositol 4,5-bisphosphate (PIP2), protects against obesity-induced diabetes in both dietary (high fat diet) and genetic (db/db mice) models of type 2 diabetes (25). This evidence concerns the gene PTEN and obesity due to melanocortin 4 receptor deficiency.