Hepatic Glucagon Action - Beyond Glucose Mobilization

Physiol Rev. 2024 Feb 1. doi: 10.1152/physrev.00028.2023. Online ahead of print.ABSTRACTGlucagon's ability to promote hepatic glucose production has been known for over a century with initial observations touting this hormone as a diabetogenic agent. However, glucagon receptor agonism (when balanced with an incretin, including glucagon-like peptide 1 (GLP-1) to dampen glucose excursions) is now being developed as a promising therapeutic target in the treatment of metabolic diseases, like metabolic dysfunction-associated steatotic disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH), and may also have benefit for obesity and chronic kidney disease. Conventionally regarded as the opposing tag-team partner of the anabolic mediator insulin, glucagon is gradually emerging as more than just a 'catabolic hormone'. Glucagon action on glucose homeostasis within the liver has been well characterized. However, growing evidence, in part thanks to new and sensitive 'omics' technologies, has implicated glucagon as more than just a 'glucose liberator'. Elucidation of glucagon's capacity to increase fatty acid oxidation while attenuating endogenous lipid synthesis speaks to the dichotomous nature of the hormone. Furthermore, glucagon action is not limited to just glucose homeostasis and lipid metabolism, as traditionally reported. Glucagon plays key regulatory roles in hepatic amino acid and ketone body metabolism, as well as mitochondrial turnover and function, indicating b...
Source: Physiological Reviews - Category: Physiology Authors: Source Type: research