Impaired arginine, citrulline, and glutamine metabolism in type 2 diabetes: insights from a stable isotope study
Authors' conclusion
Significant dysregulation exists in Arg-Cit-Gln metabolism in T2D. Our findings suggest a working model in which increased Gln turnover stimulates gluconeogenesis, increases Gln consumption, and reduces Cit availability for Arg and NO synthesis, thereby contributing to metabolic dysregulation in T2D. Interventions targeting Gln-driven gluconeogenesis while increasing Cit availability may benefit T2D management.
Study context
- Population
- Individuals with T2D and controls, overnight fasting; 59.5% female, mean age 64.4 (7.5) years, BMI 33.0 (4.3) kg/m²
- Participants
- 42 individuals
- Comparison
- T2D vs controls
- T2Dn = 21
- Controlsn = 21reference
- Outcome
- Arg, Cit and Gln metabolism (plasma concentrations and whole-body production)
Methodological detailsstable isotope tracer, compartmental analysis
- Stable isotope tracer
- Compartmental analysis
Main finding
As reported in the abstract
- T2D had lower citrulline (Cit) intracellular production, higher glutamine (Gln) clearance and intracellular pool size, and a trend toward higher arginine (Arg) clearance
- T2D vs Controls: P = 0.007
- T2D vs Controls: P = 0.002
- T2D vs Controls: P = 0.002
- T2D vs Controls: P = 0.004
- T2D vs Controls: P = 0.037
- T2D vs Controls: P = 0.017
Original publication
Impaired arginine, citrulline, and glutamine metabolism in type 2 diabetes: insights from a stable isotope study. J Clin Endocrinol Metab. Published 8 February 2026. doi:10.
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