[Effect of casein and protamine on the enzymatic degradation and the orally hypoglycemic action of insulin].
OBJECTIVE
To study the protection of casein and protamine against degradation of insulin (INS) by proteolysis enzymes and the effect of these two kinds of protein on the hypoglycemic action of INS solution and enteric-microspheres after administrated orally to rats.


METHODS
HPLC was used to determine the remained INS in the solution of alpha-chymotrypsin and trypsin with or without casein or protamine; INS solution and enteric-microspheres were prepared and adiministrated orally to rats together with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC). At the same time, casein or protamine or both of these two kinds of protein were administrated together in order to study their influence on the hypoglycemic effect of INS and microspheres.


RESULTS
Casein had a good protection against degradation of INS by alpha-chymotrypsin, but protamine had no protection effect. However, the degradation of INS by trypsin is concerned, the protection effect of protamine on INS was better that of casein. Both of protamine and casein can increase the hypoglycemic effect of INS solution and enteric-microspheres. Co-administrated these two kinds of protein had a better effect. In addition, co-administrated with SNAC, casein and protamine, INS enteric-microspheres had a longer and more potent hypoglycemic effect than that of the solution.


CONCLUSIONS
Casein and protamine can increase the stability of INS in the intestinal fluid by the mechanism of competition and combine with proteolysis enzymes, which will benefit to INS oral administration.
Qi
Rong
R
China Pharmaceutical University, Nanjing 210009, China.
Ping
Qi-neng
QN
Xu
Rui-yang
RY
Shi
Yong-ping
YP
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002210:Caprylates; D002364:Caseins / Q000494:pharmacology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008863:Microspheres; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D014357:Trypsin / Q000494:pharmacology
D001786:Blood Glucose; D002210:Caprylates; D002364:Caseins; D007004:Hypoglycemic Agents; D007328:Insulin; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D011479:Protamines; D012996:Solutions; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D014357:Trypsin