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标题：Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells
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作者：Emilie Elmelund ; Katrine D. Galsgaard ; Christian D. Johansen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：11
页码：1-20
DOI：10.1016/j.isci.2022.105296
语种：English
出版社：Elsevier
摘要：SummaryThe pancreatic hormone, glucagon, is known to regulate hepatic glucose production, but recent studies suggest that its regulation of hepatic amino metabolism is equally important. Here, we show that chronic glucagon receptor activation with a long-acting glucagon analog increases amino acid catabolism and ureagenesis and causes alpha cell hypoplasia in female mice. Conversely, chronic glucagon receptor inhibition with a glucagon receptor antibody decreases amino acid catabolism and ureagenesis and causes alpha cell hyperplasia and beta cell loss. These effects were associated with the transcriptional regulation of hepatic genes related to amino acid uptake and catabolism and by the non-transcriptional modulation of the rate-limiting ureagenesis enzyme, carbamoyl phosphate synthetase-1. Our results support the importance of glucagon receptor signaling for amino acid homeostasis and pancreatic islet integrity in mice and provide knowledge regarding the long-term consequences of chronic glucagon receptor agonism and antagonism.Graphical abstractDisplay OmittedHighlights•Glucagon receptor agonism increases amino acid catabolism and hepatic CPS-1 activity•Glucagon receptor signaling regulates the number of pancreatic alpha cells•Glucagon regulates the hepatic transcription of genes involved in amino acid metabolismBiological sciences; Endocrinology; Transcriptomics.