Glucose Sensing in L Cells: A Primary Cell Study

Cell Metab. 2008 Dec;8(6):532-9. doi: 10.1016/j.cmet.2008.11.002.

Abstract

Glucagon-like peptide-1 (GLP-1) is an enteric hormone that stimulates insulin secretion and improves glycaemia in type 2 diabetes. Although GLP-1-based treatments are clinically available, alternative strategies to increase endogenous GLP-1 release from L cells are hampered by our limited physiological understanding of this cell type. By generating transgenic mice with L cell-specific expression of a fluorescent protein, we studied the characteristics of primary L cells by electrophysiology, fluorescence calcium imaging, and expression analysis and show that single L cells are electrically excitable and glucose responsive. Sensitivity to tolbutamide and low-millimolar concentrations of glucose and alpha-methylglucopyranoside, assessed in single L cells and by hormone secretion from primary cultures, suggested that GLP-1 release is regulated by the activity of sodium glucose cotransporter 1 and ATP-sensitive K(+) channels, consistent with their high expression levels in purified L cells by quantitative RT-PCR. These and other pathways identified using this approach will provide exciting opportunities for future physiological and therapeutic exploration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Calcium / chemistry
  • Calcium / metabolism
  • Electrophysiology
  • Enteroendocrine Cells / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucokinase / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • KATP Channels / physiology
  • Mice
  • Mice, Transgenic

Substances

  • KATP Channels
  • Glucagon-Like Peptide 1
  • Glucokinase
  • Glucose
  • Calcium