Pharmaceutical Research

, Volume 11, Issue 10, pp 1496–1500

Effects of Various Protease Inhibitors on the Intestinal Absorption and Degradation of Insulin in Rats

  • Akira Yamamoto
  • Toshio Taniguchi
  • Kaori Rikyuu
  • Tomoko Tsuji
  • Takuya Fujita
  • Masahiro Murakami
  • Shozo Muranishi


The effects of protease inhibitors on the intestinal absorption of insulin were investigated in situ in closed small and large intestinal loops in rats, and the stability of insulin was examined in homoge-nates of the small and large intestine. The intestinal absorption of insulin was evaluated by its hypoglycemic effect. When insulin alone was administered into small or large intestinal loops, no marked hypoglycemic response was observed in either region. Of the coadministered protease inhibitors, soybean trypsin inhibitor (1.5, 10 mg/ml) marginally promoted insulin absorption from the large intestine, whereas aprotinin (10 mg/ml) did to a moderate degree. However, a significant hypoglycemic effect was obtained following large intestinal administration of insulin with 20 mM of Na-glycocholate, camostat mesilate and bacitracin, when compared with the controls. In contrast, we found little hypoglycemic effect following small intestinal coadministration of insulin with these protease inhibitors. In the stability experiment, bacitracin, camostat mesilate and Na-glycocholate were effective in reducing insulin degradation in both small and large intestinal homogenates. It was found that the reduction in the proteolytic rate of insulin was related to the decrease in plasma glucose concentration by these protease inhibitors in the large intestine. These findings suggest that coadministration of protease inhibitors would be useful for improving the large intestinal absorption of insulin.

insulin protease inhibitors intestinal absorption hypoglycemic effect regional difference 


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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Akira Yamamoto
    • 1
  • Toshio Taniguchi
    • 1
  • Kaori Rikyuu
    • 1
  • Tomoko Tsuji
    • 1
  • Takuya Fujita
    • 1
  • Masahiro Murakami
    • 1
  • Shozo Muranishi
    • 1
  1. 1.Department of BiopharmaceuticsKyoto Pharmaceutical UniversityMisasagi, Yamashina-kuJapan

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