Nateglinide Stimulates Glucagon-Like Peptide-1 Release by Human Intestinal L Cells via a KATP Channel-Independent Mechanism

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Author(s)

Abstract

A reduced incretin effect is one of the well-known characteristics of patients with type 2 diabetes, and impaired release of glucagon-like peptide-1 (GLP-1) has been reported to be at least partly involved. In this study, we investigated the effect of nateglinide on GLP-1 release <i>in vivo</i> and <i>in vitro</i>. The GLP-1 level in the portal blood at 20 min after oral administration of nateglinide to Wistar rats was about twice that in vehicle-treated rats. To clarify whether this effect of nateglinide was related to direct stimulation of intestinal cells, <i>in vitro</i> studies were performed using human intestinal L cells (NCI-H716). Nateglinide stimulated GLP-1 release in a concentration-dependent manner from 500 μ<small>M</small>, along with transient elevation of the intracellular calcium level. However, diazoxide, nitrendipine, and dantrolene did not block this effect of nateglinide. In addition, the major metabolite of nateglinide, tolbutamide, and mitiglinide, all of which augment insulin secretion by the pancreatic islets, had no effect on GLP-1 release by this cell line. On the other hand, capsazepine significantly inhibited the promotion of GLP-1 release by nateglinide in a concentration-dependent manner. These findings indicate that nateglinide directly stimulates GLP-1 release by intestinal L cells in a <i>K</i><sub>ATP</sub> channel-independent manner. A novel target of nateglinide may be involved in increasing intracellular calcium to stimulate GLP-1 release, <i>e.g.</i>, the transient receptor potential channels. Taken together, the present findings indicate that promotion of GLP-1 release from intestinal L cells may be another important mechanism by which nateglinide restores early-phase insulin secretion and regulates postprandial glucose metabolism.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 34(5), 671-676, 2011

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130000657778
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    11057873
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
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