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Updated: Jan 19, 2026
16:59
Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
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FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection
Santhosh Karanth1,2,3, Bhagirath Chaurasia1,2,3, Faith M Bowman1,2,4
1University of Utah Molecular Medicine Program, Salt Lake City, Utah.
Physiological Reports
|September 26, 2019
Summary
The FOXN3 gene regulates fasting blood glucose by controlling liver gene expression. Decreasing liver FOXN3 lowers blood glucose and improves glucose tolerance in mice.
Area of Science:
- Genetics
- Metabolic Regulation
- Endocrinology
Background:
- The FOXN3 gene locus is linked to fasting blood glucose levels in humans.
- Genetic variations in FOXN3 affect FOXN3 protein and transcript levels in hepatocytes.
- Previous studies in zebrafish identified FOXN3 as a transcriptional repressor influencing glucose metabolism and pancreatic alpha cell function.
Purpose of the Study:
- To investigate the metabolic effects of reduced liver FOXN3 expression in adult mice.
- To assess the impact of FOXN3 on glucose homeostasis and substrate utilization.
Main Methods:
- Adeno-associated virus serotype 8 (AAV8) mediated knockdown of liver Foxn3 expression in adult mice.
- Measurement of fasting glucose, glucagon, and insulin levels.
- Dynamic endocrine tests including glucose, insulin, pyruvate, glutamine, and glucagon challenges.
- Analysis of gluconeogenic and amino acid catabolic gene expression in the liver.
Main Results:
- Liver Foxn3 knockdown decreased fasting glucose and increased Myc expression.
- Mice with reduced liver Foxn3 exhibited improved glucose tolerance.
- Pyruvate and glutamine tolerance were reduced, with altered expression of amino acid transporters and catabolic enzymes.
- Fasting glucagon, insulin, insulin tolerance, and glucagon challenge response remained unchanged.
Conclusions:
- Liver FOXN3 plays a role in regulating substrate selection for gluconeogenesis.
- FOXN3 influences glucose metabolism through modulation of Myc expression and amino acid metabolism.
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