An 11-year-old boy with Type 1 diabetes is brought to the ER 1 hour after awakening from sleep at midnight in a cold sweat. He is confused and poorly responsive. He is normally given 4 injections of insulin daily, and the last injection was administered by his mother before he went to bed. Measurement of his blood glucose concentration indicates it is 37 mg/dL. Following an injection of glucagon, his serum glucose concentration increases to 145 mg/dL, and he shows clinical improvement. The beneficial effect of glucagon in this patient results from which of the following actions of this hormone in the liver?

Question

Quizplus · Accepted Answer

Glucagon acts by stimulating adenylate cyclase in the liver, which increases cAMP levels and activates protein kinase A, leading to glycogenolysis and gluconeogenesis, thereby raising blood glucose levels.  When glucagon binds to its receptor on hepatocytes it triggers the activation of a G-protein that in turn activates adenylate cyclase. The activation of adenylate cyclase results in increased production of cAMP which then activates PKA. Activated PKA results in phosphorylation of numerous substrates in the hepatocyte that dramatically increases glycogen breakdown and the activation of the gluconeogenic pathway. Both of these events lead to increased glucose release from the liver accounting for the observed increase in blood glucose.

An 11-Year-Old Boy with Type 1 Diabetes Is Brought to the ER