Blood glucose change after surgical administration of insulin formula into rat intestinal regions

Rat의 intestine 각 부위에 수술적으로 투여 된 insulin 제제에 의한 혈당 변화

  • 김남중 (LGCI 생명과학기술연구원 동물의약연구소) ;
  • 김명철 (충남대학교 수의과대학)
  • Accepted : 2002.05.28
  • Published : 2002.06.29


The present study was carried out to examine the effect of insulin formula on blood glucose change in normal Sprague-Dawley male rats. Also, this study was performed to investigate the feasibility of oral insulin formula development. To administrate the insulin formula into intestine, the surgical technique, celiotomy, was performed in rats. Insulin formula was administrated at a dose of 24.5 IU/kg via duodenum, ileum, and colon of the rats, and the blood glucose level was measured. For the comparison, the vehicle without insulin was administrated into ileum via celiotomy. Also, this insulin formula was administrated into rats orally using sonde and the same parameter was treasured. The bloods of all groups were collected from tail veins using syringes at given time interval. Orally administrated group did not show the change of blood glucose level and control group slightly show the change of blood glucose level at 1 hour after celiotomy. All intestinally administrated groups showed the change of blood glucose level. Among the tested groups, ileac administration group and colonic administration group showed the significant change of blood glucose level. Particularly, ileac administration group showed the lowest blood glucose level. To calculate the bioavailability of intestinal and oral administration, insulin solution was injected subcutaneosly, common insulin injection route, into another normal rats. The bioavailability of ileac group was 8.3% when compared with subcutaneous injection, duodenal group was 1.8%, colonic group was 4.2%, and oral group was 0.2%, respectively.


  1. Foster TP. Protein/peptide veterinary formulations. In: Development and formulation of veterinary dasage forms, 2nd ed. New York: Marcel Dekker, 231-282, 1998
  2. Charman SA, McLennan DN, Edwards GA et al. Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model. Pharm Res, 18(11):1620-6, 2001
  3. Tokihiro K, Arima H, Tajiri S et al. Improvement of subcutaneous bioavailability of insulin by sulphobutylether beta-cyclodextrin in rats. J Pharm Pharmacol, 52(8):911-7, 2000
  4. Heinemann L, Pfutzner A, Heise T. Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery. Curr Pharm Des, 7(14):1327-51, 2001
  5. Wang H, Li Y, Sun Q et al. Oral administration of insulin to female nonobese diabetic mice inhibited diabetes and induced Fas ligand expression on islets of Langerhans. Chin Med J (Engl), 113(5):433-436, 2000
  6. Ishida M, Machida Y, Nambu N et al. New mucosal dosage form of insulin. Chem Pharm Bull, 29:810-816, 1981
  7. Levitan DM. Transplantation for the treatment of diabetes mellitus. Semin Vet Med Surg (Small Anim), 12(4):268-273, 1997
  8. Longenecker JP, Moses AC, Flier JS et al. Effects of sodium taurodihydrofusidate on nasal absorption of insulin in sheep. J Pharm Sci, 76(5):351-355, 1987
  9. Galinsky AM. Composition and method for making a suppository for introducing a hypoglycemic agent into a mammal. US Patent 4164573, 1979
  10. Bai JP, Chang LL, Guo JH. Effects of polyacrylic polymers on the degradation of insulin and peptide drugs by chymotrypsin and trypsin. J Pharm Pharmacol, 48(1):17-21, 1996
  11. Kidron M, Ziv E, Bar-On H et al. Pharmaceutical compositions containing insulin. US Patent 4579730, 1986
  12. Radwan MA. Enhancement of absorption of insulin loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats. Drug Dev Ind Pharm, 27(9):981-989, 2001
  13. Murthy KS, Kubert DA, Fawzi MB. In vitro release characteristics of hard shell capsule products coated with aqueous- and organic-based enteric polymers. J Biomater Appl, 3(1):52-79, 1988
  14. Thomson AB, Kirdeikis P, Lastiwka R et al. Pharmacokinetics and pharmacodynamics during treatment with the omeprazole 20 mg enteric-coated tablet and 20 mg capsule in asymptomatic duodenal ulcer patients. Can J Gastroenterol, 11(8):657-660, 1997
  15. Fernandez-Moreno MD, Serrano-Rios M, Prieto JC. Identification of insulin receptors in epithelial cells from duodenum, jejunum, ileum, caecum, colon and rectum in the rat Diabete Metab, 13(2):135-139, 1987