INS and Hyperinsulinemia: Insulin receptor knockout or suppression in individual organs in mice results in severely impaired glucose uptake in skeletal muscle; decreased fat storage in adipose tissue with normal levels of glucose and fatty acids in circulation; increased gluconeogenesis in the liver accompanied with systemic insulin resistance, hyperinsulinemia and glucose intolerance; decreased islet beta-cell proliferation and insulin secretion, and insulin receptor knockout in neurons increase appetite.104