Insulin is a hormone with various metabolic effects such as glucose uptake and glycogen synthesis in insulin's target tissues. Skeletal muscle has been considered to be a principal site of insulin resistance in type 2 diabetes. Studies of mice with muscle specific-knockout of the insulin receptor demonstrated that although skeletal muscle was insulin resistant, glucose tolerance was near normal at the whole body, indicating the possible importance of liver. beta cell specific disruption of the insulin receptor indicated that primary insulin resistance at the beta cells resulted in a defect of insulin secretion and impaired glucose tolerance. These animal models suggest that a combination of insulin resistance in muscle, liver, adipose cells, and beta cells appears to create the phenotype of type 2 diabetes.