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Region-Dependent Role of the Mucous/Glycocalyx Layers in Insulin Permeation Across Rat Small Intestinal Membrane

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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 (Papp) of insulin for the hyaluronidase-pretreated group was significantly increased compared to the PBS-pretreated (control) group in all small intestinal regions, and the Papp 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 Papp 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.

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Acknowledgments

The authors are grateful to Mr. Yoshifumi Kaneko for his work on light microscopy. The Ministry of Education, Culture, Sports, Science, and Technology, Japan partly supported this research.

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Authors and Affiliations

  1. Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo, 142-8501, Japan

    Yoshinobu Aoki, Mariko Morishita & Kozo Takayama

  2. Research Center, Kyorin Pharmaceutical Co., Ltd., Nogi 1848, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan

    Yoshinobu Aoki

  3. Department of Pharmacy, Matsudo City Hospital, Kamihongou 4005, Matsudo, Chiba, 271-8511, Japan

    Kazunori Asai

  4. Department of Pathology, Matsudo City Hospital, Kamihongou 4005, Matsudo, Chiba, 271-8511, Japan

    Bunshiro Akikusa & Shuji Hosoda

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  1. Yoshinobu Aoki
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  2. Mariko Morishita
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Correspondence to Mariko Morishita.

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Aoki, Y., Morishita, M., Asai, K. et al. Region-Dependent Role of the Mucous/Glycocalyx Layers in Insulin Permeation Across Rat Small Intestinal Membrane. Pharm Res 22, 1854–1862 (2005). https://doi.org/10.1007/s11095-005-6137-z

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