title: Enhanced bioavailability of subcutaneously injected insulin coadministered with collagen in rats and humans.
abstract: The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. 125I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Hori
authors.forename: F
authors.initials: F
authors.lastname: Komada
authors.forename: S
authors.initials: S
authors.lastname: Iwakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
authors.forename: K
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D001682:Biological Availability; D003094:Collagen / Q000008:administration & dosage*; D005079:Excipients; D006323:Heart Arrest / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005079:Excipients; D007328:Insulin; D007457:Iodine Radioisotopes; D003094:Collagen