Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 56, Issue 3, Pages 201-211Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-15-0293
Keywords
GLP-1-producing cell lines; peptide production; L-cells
Categories
Funding
- Novo Nordisk Centre for Basic Metabolic Research (Novo Nordisk Foundation)
- Wellcome Trust [WT106262/Z/14/Z, WT106263/Z/14/Z]
- MRC [MRC_MC_UU_12012]
- Medical Research Council [MC_UU_12012/3] Funding Source: researchfish
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016574] Funding Source: researchfish
- MRC [MC_PC_12012] Funding Source: UKRI
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GLUTag, NCI-H716, and STC-1 are cell lines that are widely used to study mechanisms underlying secretion of glucagon-like peptide-1 (GLP-1), but the extent to which they resemble native L-cells is unknown. We used validated immunoassays for 14 different hormones to analyze peptide content (lysis samples; n = 9 from different passage numbers) or peptide secretion in response to buffer (baseline), and after stimulation with 50 mM KCl or 10 mM glucose + 10 mu M forskolin/3-isobutyl-1-methylxanthine (n = 6 also different passage numbers). All cell lines produced and processed proglucagon into GLP-1, GLP-2, glicentin, and oxyntomodulin in a pattern (prohormone convertase (PC) 1/3 dependent) similar to that described for human gut. All three cell lines showed basal secretion of GLP-1 and GLP-2, which increased after stimulation. In contrast to freshly isolated murine L-cells, all cell lines also expressed PC2 and secreted large amounts of pancreatic glucagon. Neurotensin and somatostatin storage was low and secretion was not consistently increased by stimulation. STC-1 cells released more glucose-dependent insulinotropic polypeptide than GLP-1 at baseline (P < 0.01) and KCl elevated its secretion (P < 0.05). Peptide YY, which normally co-localizes with GLP-1 in distal L-cells, was not detected in any of the cell lines. GLUTag and STC-1 cells also expressed vasoactive intestinal peptide, but none expressed pancreatic polypeptide or insulin. GLUTag contained and secreted large amounts of CCK, while NCI-H716 did not store this peptide and STC-1 contained low amounts. Our results show that hormone production in cell line models of the L-cell has limited similarity to the natural L-cells.
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