Uremia and insulin resistance: N-carbamoyl-asparagine decreases insulin-sensitive glucose uptake in rat adipocytes

Kidney Int. 2004 Mar;65(3):881-7. doi: 10.1111/j.1523-1755.2004.00456.x.


Background: In uremia, urea-derived cyanate reacts with amino groups irreversibly forming carbamoyl amino acids (C-AA) and carbamoyl proteins. Carbamoylated molecules can affect binding and trafficking and alter metabolic pathways. The C-AA role in insulin-sensitive glucose transport has not been explored and may contribute to insulin resistance in uremia.

Methods: Insulin-stimulated glucose uptake by cultured rat adipocytes was measured using both 3-minute and 3-second assays. Adipocytes were incubated for 24 hours in medium containing 0.5 micromol/mL of 15 different C-AA. 125I-insulin binding studies were done. C-asparagine in plasma from 10 uremic patients on continuous ambulatory peritoneal dialysis (CAPD) was measured using high-performance liquid chromatography (HPLC).

Results: Insulin-sensitive glucose uptake was reduced 34% by N-carbamoyl-l-asparagine, (N-C-Asn), in a dose-dependent manner with a half-maximally effective concentration of 0.15 micromol/mL. Fourteen other N-carbamoyl-amino acids as well as 0.5 micromol/mL of asparagine did not affect insulin sensitive glucose uptake. N-C-Asn, l-asparagine, and the other N-carbamoyl amino acids (0.5 micromol/mL) had no effect on basal glucose uptake. These data suggest that that N-C-Asn affects the insulin sensitive glucose transporter system. 125I-insulin binding studies demonstrated that N-C-Asn did not alter insulin binding. Glucose uptake measured using a 3-second assay showed that the glucose affinity of the transporter and glucose phosphorylation were not affected. In uremic patients managed by CAPD, the mean free N-C-Asn plasma level was 1.33 micromol/mL.

Conclusion: These data suggest that N-C-Asn concentration may contribute to the insulin resistance seen in uremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Asparagine / analogs & derivatives*
  • Asparagine / chemistry
  • Asparagine / pharmacokinetics
  • Cells, Cultured
  • Glucose / pharmacokinetics*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Insulin / pharmacokinetics
  • Insulin Resistance / physiology*
  • Iodine Radioisotopes
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / therapy
  • Male
  • Monosaccharide Transport Proteins / metabolism
  • Peritoneal Dialysis, Continuous Ambulatory
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Uremia / metabolism*


  • Hypoglycemic Agents
  • Insulin
  • Iodine Radioisotopes
  • Monosaccharide Transport Proteins
  • Asparagine
  • Glucose