However, previous studies in mice have shown that increasing IR in obesity is associated with a receptor-level defect and internal changes in the insulin signaling pathway, without a significant alteration in the number of the GLUT-4 glucose transporter responsible for insulin sensitivity (Le Marchand-Brustel et al., 1999). The gene discussed is SLC2A4; the disease is obesity due to melanocortin 4 receptor deficiency.