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Enhanced glucagon response and mRNA stability in prediabetic OLETF hepatocytes

Graphical Abstract image adapted from Deguchi et al., Bioscience, Biotechnology, and Biochemistry (2025), DOI: [10.1093/bbb/zbaf133]. © Oxford University Press. Used with permission.

Credit: Osaka Metropolitan University / Oxford University Press

Glucagon dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), yet its early hepatic effects remain unclear.

Here, Osaka Metropolitan University researchers demonstrate that glucagon-induced gluconeogenesis is markedly enhanced in primary hepatocytes from prediabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a well-established model of human T2DM. Compared to control LETO rats, OLETF hepatocytes showed significantly higher glucagon-stimulated expression of gluconeogenic genes at both mRNA and protein levels, along with elevated glucose production.

Notably, mRNA decay analysis revealed prolonged half-lives of gluconeogenic transcripts in OLETF hepatocytes, indicating enhanced mRNA stability as a novel mechanism contributing to increased hepatic glucose output.

These findings highlight aberrant glucagon responsiveness and post-transcriptional regulation as potential predisposing factors in genetically susceptible models prior to the onset of overt metabolic abnormality, suggesting may be of interest for preventive or therapeutic strategies for controlling fasting hyperglycemia.

Paper information

Journal: Bioscience, Biotechnology, and Biochemistry
Title: Augmented glucagon-induced gluconeogenesis in primary hepatocytes from Otsuka Long-Evans Tokushima Fatty rats 
DOI: 10.1093/bbb/zbaf133
Authors: Miwako Deguchi, Akemi Hosoda, Tomoe Fukumura, Shigeru Saeki, DongHo Kim
Published: 10 September 2025
URL: https://doi.org/10.1093/bbb/zbaf133

Contact

Miwako Deguchi
Graduate School of Human Life and Ecology
Email: deguchi[at]omu.ac.jp

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