Glucose Sensing in L Cells: A Primary Cell Study

By F. Reimann, A. Habib, G. Tolhurst, H. Parker, G. J. Rogers, F. Gribble. Cell Metabolism, 2008

758 citations recorded by the source corpus.

Summary 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 α-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.

Subfields: Molecular Biology, Nutrition and Dietetics, Surgery

View Paper: https://www.semanticscholar.org/paper/770bdd1d69fb5463b145fc6871e6f070aa89baa3

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In Molecular Biology

1. M. Nauck
2. T. Preston
3. G. Gibson
4. D. J. Drucker
5. Johan Auwerx
6. D. Morrison

In Nutrition and Dietetics

1. K. Murphy
2. Matthias Tschöp
3. Stephen R. Bloom

In Surgery

1. M. Nauck
2. D. J. Drucker
3. F. Reimann
4. Johan Auwerx
5. F. Gribble
6. J. Y. Chiang
7. Ralph DeFronzo
8. J. Meier

Citations in the corpus

• Glucagon-like peptide 1 (GLP-1) (2019, background): “In contrast, there is no effect of sucralose on GLP-1 secretion in primary L-cell cultures in other reports [281,282], and infusion of artificial sweeteners does not affect glucose-stimulated GLP-1 secretion in healthy human volunteers [283,284].”
• Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults (2014, methodology): “The effect of propionate on PYY and GLP-1 release from human colonic crypts was determined using a modi fi ed version of an established method 32 (see online supplementary material).”
• Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2 (2012, methodology): “Secreted and cellular GLP-1 was extracted as previously described (24), and active GLP-1 was quantified by ELISA (Millipore).”
• Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells (2011, neutral): “Finally, FACS sorting of alpha cells from transgenic mice fed on a high-fat diet expressing a yellow fluorescent protein under the control of the glucagon promote”
• TGR5-mediated bile acid sensing controls glucose homeostasis. (2009, background): “, 2006), and inspired by the fact that TGR5 is expressed in enteroendocrine cells (Katsuma et al., 2005; Reimann et al., 2008), we explored in this study whether TGR5 activation could alter glucose homeostasis.”
• Na+-d-glucose Cotransporter SGLT1 is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion (2011, background): “Earlier in vitro studies have demonstrated that SGLT1-mediated monosaccharide transport triggers incretin secretion via the electrogenic coupled influx of Na, which results in membrane depolarization, electrical activity, voltage-gated Ca entry, and exocytosis (16,42), although the contribution of t”