In obesity-related glucose metabolism, which hormone signal often increases to trigger hepatic glucose output?

• A. Insulin
• B. Glucagon
• C. Cortisol
• D. Adiponectin

Answer: (B)

Glucagon is the signal that drives hepatic glucose output. It acts on liver cells to raise blood glucose by stimulating both glycogen breakdown and glucose production through gluconeogenesis. In obesity, insulin resistance reduces the liver’s responsiveness to insulin, so insulin’s usual suppression of hepatic glucose production is diminished. This makes the glucagon signal more influential, and the liver increases glucose release to the bloodstream. Glucagon works through its receptor to raise cAMP, activating PKA, which promotes glycogenolysis and the expression of gluconeogenic enzymes like PEPCK and G6Pase. While cortisol can also boost hepatic glucose production, and adiponectin levels drop in obesity (which worsens insulin resistance), the classic and most direct trigger for hepatic glucose output in this context is increased glucagon signaling.