title: Region-dependent role of the mucous/glycocalyx layers in insulin permeation across rat small intestinal membrane.
abstract: The regional difference in the contribution of the mucous/glycocalyx layers in rat small intestine, as a diffusional or enzymatic barrier, to the absorption of insulin was investigated by in vitro studies. The mucous/glycocalyx layers from the duodenum, the jejunum, and the ileum in rat were successfully removed without damaging membrane integrity, by exposing them to a hyaluronidase solution in situ. In an in vitro transport experiment, the apparent permeability coefficient (P(app)) of insulin for the hyaluronidase-pretreated group was significantly increased compared to the PBS-pretreated (control) group in all small intestinal regions, and the P(app) of insulin in both PBS- and hyaluronidase-pretreated groups increased in the following order: duodenum < jejunum < ileum. On the other hand, irrespective of small intestinal regions, the P(app) of FD-4 and of antipyrine, respectively the passive para- and transcellular permeation marker, exhibited no significant differences between PBS- and hyaluronidase-pretreated group. In addition, a significant amount of insulin was degraded in the mucous/glycocalyx layers compartment removed by hyaluronidase pretreatment, and the degradation activity in the mucous/glycocalyx layers showed regional differences in the following order: duodenum > jejunum > ileum. These findings suggest that, irrespective of small intestinal regions, the mucous/glycocalyx layers contributed to insulin permeation predominantly as an enzymatic barrier, and not as a diffusional barrier. Furthermore, the variation of the enzymatic activities in the mucous/glycocalyx layers and in the brush-border membrane would be one factor that accounts for the regional differences in the transport of insulin.
authors.affiliation: Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Aoki
authors.forename: Mariko
authors.initials: M
authors.lastname: Morishita
authors.forename: Kazunori
authors.initials: K
authors.lastname: Asai
authors.forename: Bunshiro
authors.initials: B
authors.lastname: Akikusa
authors.forename: Shuji
authors.initials: S
authors.lastname: Hosoda
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D001692:Biological Transport; D004355:Drug Stability; D019276:Glycocalyx / Q000502:physiology*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007328:Insulin / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D006821:Hyaluronoglucosaminidase; D000983:Antipyrine