ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: FR-PO502

High Potassium Suppresses Glycosuria in Tubule-Specific mTORC2 Knockout Mice

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic


  • Demko, John Eric, University of California San Francisco, San Francisco, California, United States
  • Saha, Bidisha, University of California San Francisco, San Francisco, California, United States
  • Takagi, Enzo, University of California San Francisco, San Francisco, California, United States
  • Pearce, David, University of California San Francisco, San Francisco, California, United States

Insulin signaling promotes proximal tubule glucose reabsorption and suppresses gluconeogenesis (GNG). mTORC2 is critical to insulin signaling in multiple cell types and there is emerging evidence for its importance in the proximal tubule. Potassium (K) has also been shown to regulate GNG in the kidney. However, the mechanism and overall significance of the relationship between K and glucose homeostasis is poorly understood.


Rictor is an essential component of the mTORC2 complex. Inducible tubule-specific Rictor knockout (TRKO) mice were made with Pax8-rtTA TetOCre Rictorflox/flox. Mice were fasted for 18 hours then refed 4 hours before sacrifice. Mice were adapted to a 0.5% K diet prior to refeeding and then switched to either a 0.5% K or 3% K diet for refeeding. Data were obtained in metabolic cages during refeeding.


Figure 1 shows a significant decrease in urine glucose excretion after refeeding on a 3.0% K diet compared to a 0.5% K diet despite no difference in area under the curve (AUC) of serum glucose (n=6–10 per group for all experiments). TRKO mice refed with a 3.0% K diet compared to 0.5% K diet had higher serum K (mean ± standard error, 7.3±0.4 vs 4.7±0.2mEq/L; p<0.001), higher hematocrit (42.0±0.8 vs 35.7±0.6%; p<0.001), decreased refeeding weight gain (0.70±0.09 vs 2.25± 0.24g; p<0.001), decreased food intake (1.02±0.08 vs 1.92±0.19g; p<0.001), and higher urine output (0.87±0.10 vs 0.39±0.05mL; p<0.001). There were no differences in baseline weight, refeeding water intake, or BUN between TRKO mice on either diet.


High dietary K rapidly suppressed glycosuria without changing serum glucose in TRKO mice. A change in GFR or filtered load of glucose is less likely to explain the reduction in glycosuria in these short-term experiments. Dietary K appears to act through an mTORC2-independent pathway to regulate renal glucose reabsorption. Future studies will examine the role of dietary K on GNG, glucose transporters, and insulin signaling pathways.

**p<0.01; ns, not significant by t-test.


  • NIDDK Support