Imeglimin prevents visceral hypersensitivity and colonic hyperpermeability in irritable bowel syndrome rat model

Tsukasa Nozu; Saori Miyagishi; Masatomo Ishioh; Kaoru Takakusaki; Toshikatsu Okumura

doi:10.1016/j.jphs.2023.07.002

Imeglimin prevents visceral hypersensitivity and colonic hyperpermeability in irritable bowel syndrome rat model

J Pharmacol Sci. 2023 Sep;153(1):26-30. doi: 10.1016/j.jphs.2023.07.002. Epub 2023 Jul 7.

Authors

Tsukasa Nozu¹, Saori Miyagishi², Masatomo Ishioh², Kaoru Takakusaki³, Toshikatsu Okumura⁴

Affiliations

¹ Department of Regional Medicine and Education, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan; Center for Medical Education, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan; Department of General Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan. Electronic address: tnozu@sea.plala.or.jp.
² Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
³ Division of Neuroscience, Department of Physiology, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
⁴ Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan; Department of General Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.

PMID: 37524451
DOI: 10.1016/j.jphs.2023.07.002

Abstract

Visceral hypersensitivity and leaky gut, which are mediated via corticotropin-releasing factor (CRF) and Toll-like receptor 4 are key pathophysiology of irritable bowel syndrome (IBS). Metformin was reported to improve these gastrointestinal (GI) changes. In this study, we attempted to determine the effects of imeglimin, which was synthesized from metformin on GI function in IBS rat models. Imeglimin blocked lipopolysaccharide- or CRF-induced visceral hypersensitivity and colonic hyperpermeability. These effects were prevented by compound C or naloxone. These results suggest that imeglimin may be effective for the treatment of IBS by improved visceral sensation and colonic barrier via AMPK and opioid receptor.

Keywords: Colonic permeability; Imeglimin; Visceral sensation.

MeSH terms

Animals
Colon
Corticotropin-Releasing Hormone / pharmacology
Irritable Bowel Syndrome* / drug therapy
Metformin* / pharmacology
Rats

Substances

imeglimin
Corticotropin-Releasing Hormone
Metformin