INS and obesity due to melanocortin 4 receptor deficiency: Misu et al. studied the role of Sepp1 in the regulation of glucose metabolism and insulin sensitivity in KKAy mice, a model of type 2 diabetes and obesity; knockdown of Sepp1 by siRNA injection resulted in a 30% reduction in Sepp1 protein levels in the liver and blood and improved both glucose intolerance and insulin resistance [42].