Mechanisms controlling glucose-induced GLP-1 secretion in human small intestine

Emily W. Sun, Dayan De Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L. Due, David A. Wattchow, Christopher K. Rayner, Adam M. Deane, Richard Young, Damien J. Keating

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30-min intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1 levels. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in the ileum at 200 mmol/L glucose. In ex vivo tissue from the duodenum and ileum, but not the colon, 300 mmol/L glucose potently stimulated GLP-1 release. In the ileum, this response was independent of osmotic influences and required delivery of glucose via GLUT2 and mitochondrial metabolism. The requirement of voltage-gated Na+ and Ca2+ channel activation indicates that membrane depolarization occurs. KATP channels do not drive this, as tolbutamide did not trigger release. The sodium-glucose cotransporter 1 (SGLT1) substrate a-MG induced secretion, and the response was blocked by the SGLT1 inhibitor phlorizin or by replacement of extracellular Na+ with N-methyl-D-glucamine. This is the first report of the mechanisms underlying glucose-induced GLP-1 secretion from human small intestine. Our findings demonstrate a dominant role of SGLT1 in controlling glucosestimulated GLP-1 release in human ileal L cells.

Original languageEnglish
Pages (from-to)2144-2149
Number of pages6
JournalDiabetes
Volume66
Issue number8
DOIs
Publication statusPublished or Issued - Aug 2017

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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