Renal glycosuria triggers a coordinated mannose and glutamine metabolic program to maintain glucose homeostasis.

Renal glycosuria activates a coordinated mannose and glutamine metabolic program that sustains glucose homeostasis, even with significant urinary glucose loss in mice.

• Why it matters: Understanding how the body compensates for glucose loss is crucial for improving diabetes treatments and overcoming limitations of current therapies like SGLT2 inhibitors.
• What they did: Researchers studied renal Glut2 knockout mice using metabolic profiling and isotope tracing to uncover adaptations in mannose and glutamine metabolism during glycosuria, including substrate utilization shifts.
• The result: Disruption of mannose or glutamine pathways caused hypoglycemia, highlighting their role in maintaining glucose levels, and revealing a kidney-driven metabolic system that could enhance glucose-lowering strategies.