Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats.
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 homogenates 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.
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
A
A
Yamamoto
T
T
Taniguchi
K
K
Rikyuu
T
T
Tsuji
T
T
Fujita
M
M
Murakami
S
S
Muranishi
D000818:Animals; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D066298:In Vitro Techniques; D007328:Insulin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D011480:Protease Inhibitors