Work

Glucagon may be extracted across the liver by a glucagon receptor-dependent mechanism, and this is impaired in an animal model of fatty liver disease

Year: 2026

Type: article

Abstract: We identify the liver as an active glucagon-clearing organ: ∼20% of portal glucagon is extracted under physiological conditions via glucagon receptor-dependent uptake, not enzymatic cleavage. DPP-4 and neprilysin inhibition does not alter hepatic glucagon disappearance, and mass spectrometry confirms glucagon remains largely intact. Strikingly, diet-induced hepatic steatosis nearly abolishes glucagon extraction, coinciding with reduced hepatic GCGR expression, suggesting impaired receptor-mediated clearance may contribute to hyperglucagonemia in MASLD.

Source: American Journal of Physiology-Endocrinology and Metabolism

DOI: 10.1152/ajpendo.00493.2025