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Hepatic glucagon action: beyond glucose mobilization.
Kajani, Sarina; Laker, Rhianna C; Ratkova, Ekaterina; Will, Sarah; Rhodes, Christopher J.
Afiliação
  • Kajani S; Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States.
  • Laker RC; Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States.
  • Ratkova E; Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
  • Will S; Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States.
  • Rhodes CJ; Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States.
Physiol Rev ; 104(3): 1021-1060, 2024 Jul 01.
Article em En | MEDLINE | ID: mdl-38300523
ABSTRACT
Glucagon'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 broader glucagon signaling consequences for metabolic homeostasis mediated by the liver. Here we examine the broadening role of glucagon signaling within the hepatocyte and question the current dogma, to appreciate glucagon as more than just that "catabolic hormone."
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glucagon / Glucose / Fígado Limite: Animals / Humans Idioma: En Revista: Physiol Rev Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glucagon / Glucose / Fígado Limite: Animals / Humans Idioma: En Revista: Physiol Rev Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos