Lipids & metabolic liver disease
Lower glucagon response and attenuated hepatic glucagon signaling in MASLD
Authors' conclusion
Among individuals with prediabetes or type 2 diabetes, greater hepatic steatosis and inflammation are associated with lower circulating glucagon levels and attenuated hepatic glucagon signaling.
Study context
- Population
- Adults with prediabetes or T2D who underwent a 75 g oral glucose tolerance test (OGTT) with fasting and 2-h plasma glucagon; MASLD severity by noninvasive scores and transient liver elastography
- Participants
- 137 adults
- Exposure
- Glucagon response by MASLD severity
- Outcome
- Integrated glucagon response (glucagon AUC during OGTT)
- Follow-up
- 2-h OGTT
Methodological detailsliver transcriptome and single-nucleus RNA sequencing (snRNA-seq) analyses
- Liver transcriptome and snRNA-seq analyses
Main finding
As reported in the abstract
Glucagon AUC during 2-h OGTT
Moderate-to-severe steatosis vs Steatosis control: P = 0.006 · High-risk MASH vs MASH control: P = 0.014
Observational data: associations, not effects.
Further findings
Plasma glucagon and fibrosis severity
- No significant association between plasma glucagon levels and fibrosis severity
Hepatic glucagon signaling (transcriptomics)
- Downregulation of GCGR and downstream signaling pathways in MASLD liver, particularly in hepatocytes in advanced disease
Original publication
Lower glucagon response and attenuated hepatic glucagon signaling in MASLD. Diabetes Metab. Published 11 August 2026. doi:10.
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