Sustained HIF-1 overexpression in β-cells by the deletion of the Vhl gene (encoding the von Hippel–Lindau protein) causes impaired insulin secretion and glucose intolerance in mice [39,40,41], indicating that the upregulation of HIF-1α is deleterious to β-cell function and contributes to diabetes. The gene discussed is INS; the disease is Glucose intolerance.