Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells
Open accessAbstract
AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with anti-apoptotic effects on the pancreatic beta cell. The aim of this study was to generate transgenic mice with fluorescently labelled GIP-secreting K cells and to use these to investigate pathways by which K cells detect nutrients. METHODS: Transgenic mice were generated in which the GIP promoter drives the expression of the yellow fluorescent protein Venus. Fluorescent cells were purified by flow cytometry and analysed by quantitative RT-PCR. GIP secretion was assayed in primary cultures of small intestine. RESULTS: Expression of Venus in transgenic mice was restricted to K cells, as assessed by immunofluorescence and measurements of the Gip mRNA and GIP protein contents of purified cells. K cells expressed high levels of mRNA for Kir6.2 (also known as Kcnj11), Sur1 (also known as Abcc8), Sglt1 (also known as Slc5a1), and of the G-protein-coupled lipid receptors Gpr40 (also known as Ffar1), Gpr119 and Gpr120. In primary cultures, GIP release was stimulated by glucose, glutamine and linoleic acid, and potentiated by forskolin plus 3-isobutyl-1-methylxanthine (IBMX), but was unaffected by the artificial sweetener sucralose. Secretion was half-maximal at 0.6 mmol/l glucose and partially mimicked by alpha-methylglucopyranoside, suggesting the involvement of SGLT1. Tolbutamide triggered secretion under basal conditions, whereas diazoxide suppressed responses in forskolin/IBMX. CONCLUSIONS/INTERPRETATION: These transgenic mice and primary culture techniques provide novel opportunities to interrogate the mechanisms of GIP secretion. Glucose-triggered GIP secretion was SGLT1-dependent and modulated by K(ATP) channel activity but not determined by sweet taste receptors. Synergistic stimulation by elevated cAMP and glucose suggests that targeting appropriate G-protein-coupled receptors may provide opportunities to modulate GIP release in vivo.
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GLP-1 and GIP are secreted from enteroendocrine L-cells and K-cells upon glucose, fructose, amino acid and free fatty acid ingestion and potentiate insulin release through the incretin effect.
“The gut-derived hormones GLP-1 and GIP, which are secreted from enteroendocrine L-cells66 and K-cells,67 respectively, upon glucose,66, 68 fructose,69 amino acid70 and free fatty acid (FFA)71, 72 ingestion, also potentiate insulin release through the so-called incretin effect.”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [67]
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- Authors
- Parker, H. E., Habib, A. M., Rogers, G. J., Gribble, F. M., & Reimann, F.
- Affiliations
- Addenbrooke's Hospital (GB)
- Corresponding author
- Gribble, F. M.
- Reimann, F.
- Venue
- Diabetologia
- Published
- 2008-12-11
- Volume
- 52
- Issue
- 2
- Pages
- 289-298
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC4308617
- OpenAlex
- W2045343006
- Cited by
- 324
- References
- 47
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 12 · 2020: 9 · 2019: 15 · 2018: 21 · 2017: 17 · 2016: 31 · 2015: 24 · 2014: 28 · 2013: 21 · 2012: 33
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Diabetologia (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust (071187, 084210)
- Lister Institute of Preventive Medicine
- Medical Research Council
- Cambridge Institute for Medical Research, University of Cambridge
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- glucose-dependent insulinotropic polypeptide, GIP secretion, K cells, nutrient sensing, SGLT1, GPR40, GPR119, GPR120, incretins, transgenic mice, cAMP signaling, tolbutamide, diazoxide, small intestine
- MeSH terms
- Actins, Cyclic AMP, Animals, Calcium-Binding Proteins, Flow Cytometry, Gastric Inhibitory Polypeptide, Glucose, Killer Cells, Natural, Lipoproteins, Mice, Transgenic, Promoter Regions, Genetic, Receptors, Gastrointestinal Hormone, Tetradecanoylphorbol Acetate, Chromosomes, Artificial, Bacterial, Mice, Rats
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