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Glucagon acutely stimulates hepatic gluconeogenesis
Caroline Hansen1, Josephine Fisker-Andersen1, Christine Rasmussen1
1Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Peptides
|October 15, 2025
Summary
Glucagon rapidly stimulates hepatic glucose production through transcription-independent pathways, offering minute-to-minute control of glucose homeostasis.
Area of Science:
- Metabolic Regulation
- Endocrinology
- Hepatology
Background:
- Glucagon traditionally increases hepatic glucose production via gene expression.
- The acute, transcription-independent effects of glucagon on gluconeogenesis were uncertain.
Purpose of the Study:
- To investigate the acute, transcription-independent effects of glucagon on hepatic gluconeogenesis and glucose output.
Main Methods:
- Utilized an in situ perfused mouse liver model.
- Measured hepatic glucose output in response to glucagon and gluconeogenic substrates.
Main Results:
- Glucagon acutely increased hepatic glucose production within minutes, independent of transcription and glycogen.
- Co-administration of glucagon with gluconeogenic substrates further enhanced glucose output.
Conclusions:
- Glucagon acts as a rapid metabolic modulator, controlling hepatic glucose output on a minute-to-minute basis.
- Findings challenge the traditional view of glucagon solely as a transcriptional regulator.
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