Hepatic steatosis-and not type 2 diabetes, body mass index or hepatic fibrosis-associates with hyperglucagonemia in individuals with steatotic liver disease

Increased plasma concentrations of glucagon (hyperglucagonemia) are reported in patients with type 2 diabetes (T2D) and are considered a diabetogenic risk factor. Emerging evidence suggests that hepatic steatosis in obesity is causing a condition of resistance toward glucagon's effects on amino acid metabolism, resulting in an amino acid-induced hyperglucagonemia. We investigated the presence of hyperglucagonemia in individuals with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD), and whether body mass index (BMI), T2D, hepatic steatosis, and/or fibrosis contribute to this relationship. To dissect potential mechanisms, we also determined hepatic gene expression related to amino acid transport and catabolism. Individuals with MASLD had hyperglucagonemia {controls (