Blood glucose-lowering activity of a hyaluronan-insulin complex after oral administration to rats with diabetes

Diabetes Technol Ther. 2005 Dec;7(6):948-57. doi: 10.1089/dia.2005.7.948.


Background: Several covalently modified insulin derivatives or formulations with absorption enhancers have been shown to decrease the blood glucose concentration after oral administration in animals with diabetes. The aim of this study was to investigate the biological activity of a novel hyaluronan-insulin complex.

Methods: The efficacy of the complexed insulin after oral and subcutaneous administration was evaluated by analysis of blood glucose concentrations in rats with streptozotocin-induced diabetes.

Results: The complexed insulin significantly decreased blood glucose concentrations within 1 h after oral administration in eight of 10 rats in the dose interval 1.5-4.7 mg (3.1-14.5 mg/kg). Oral administration of native insulin or non-complexed insulin plus hyaluronan using similar doses failed to decrease blood glucose concentrations. The lowest oral dose of complexed insulin achieving a statistically significant decrease in blood glucose concentrations was 1.2-1.5 mg (about 4 mg/kg), and the threshold dose after subcutaneous administration was 0.08-0.12 mg (0.25 mg/kg).

Conclusions: The hyaluronan-insulin complex was active after oral administration and decreased blood glucose concentrations in rats with streptozotocin-induced diabetes. The ratio between the oral and subcutaneous threshold doses was about 16.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Dose-Response Relationship, Drug
  • Hyaluronic Acid / pharmacology*
  • Injections, Subcutaneous
  • Insulin / pharmacology*
  • Linear Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin


  • Blood Glucose
  • Insulin
  • Streptozocin
  • Hyaluronic Acid