Hyperglycemia in rodent models of type 2 diabetes requires insulin-resistant alpha cells

Significance Diet-induced type 2 diabetes (T2D) is becoming a worldwide epidemic. Patients with T2D fail to respond to insulin normally and have elevated blood glucose and insulin. In autoimmune diabetes, blood glucose is elevated due to uncontrolled glucagon, a hormone normally suppressed and opposed by insulin. To study the role of glucagon in T2D, rodent models of the disease were created lacking glucagon action. These animals failed to develop hyperglycemia unless glucagon action was restored or the animals were given the high concentrations of insulin typical of animals with T2D. This indicates that the unopposed glucagon action in T2D is necessary to support elevated blood glucose of diabetes. Suppressing glucagon or its action may benefit patients with T2D.