42
views
0
recommends
+1 Recommend
2 collections
    0
    shares

          The flagship journal of the Society for Endocrinology. Learn more

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cellular mechanisms of incretin hormone secretion

      review-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Enteroendocrine cells located along the gastrointestinal epithelium sense different nutrients/luminal contents that trigger the secretion of a variety of gut hormones with different roles in glucose homeostasis and appetite regulation. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are involved in the regulation of insulin secretion, appetite, food intake and body weight after their nutrient-induced secretion from the gut. GLP-1 mimetics have been developed and used in the treatment of type 2 diabetes mellitus and obesity. Modulating the release of endogenous intestinal hormones may be a promising approach for the treatment of obesity and type 2 diabetes without surgery. For that reason, current understanding of the cellular mechanisms underlying intestinal hormone secretion will be the focus of this review. The mechanisms controlling hormone secretion depend on the nature of the stimulus, involving a variety of signalling pathways including ion channels, nutrient transporters and G-protein-coupled receptors.

          Related collections

          Most cited references131

          • Record: found
          • Abstract: found
          • Article: not found

          A single-cell survey of the small intestinal epithelium

          Intestinal epithelial cells (IECs) absorb nutrients, respond to microbes, provide barrier function and help coordinate immune responses. We profiled 53,193 individual epithelial cells from mouse small intestine and organoids, and characterized novel subtypes and their gene signatures. We showed unexpected diversity of hormone-secreting enteroendocrine cells and constructed their novel taxonomy. We distinguished between two tuft cell subtypes, one of which expresses the epithelial cytokine TSLP and CD45 (Ptprc), the pan-immune marker not previously associated with non-hematopoietic cells. We also characterized how cell-intrinsic states and cell proportions respond to bacterial and helminth infections. Salmonella infection caused an increase in Paneth cells and enterocytes abundance, and broad activation of an antimicrobial program. In contrast, Heligmosomoides polygyrus caused an expansion of goblet and tuft cell populations. Our survey highlights new markers and programs, associates sensory molecules to cell types, and uncovers principles of gut homeostasis and response to pathogens.
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2

            Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1–secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.
              • Record: found
              • Abstract: found
              • Article: not found

              High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

              Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

                Author and article information

                Journal
                J Mol Endocrinol
                J Mol Endocrinol
                JME
                Journal of Molecular Endocrinology
                Bioscientifica Ltd (Bristol )
                0952-5041
                1479-6813
                22 February 2024
                19 January 2024
                01 May 2024
                : 72
                : 4
                : e230112
                Affiliations
                [1 ]Institute of Metabolic Science , Addenbrooke’s Hospital, Cambridge, UK
                Author notes
                Correspondence should be addressed to F Reimann or F M Gribble: fr222@ 123456cam.ac.uk or fmg23@ 123456cam.ac.uk

                This paper forms part of a special collection on the theme of Incretins. The guest editors for this collection were Timo Müller and Erin Mulvihill.

                Author information
                http://orcid.org/0000-0001-9399-6377
                Article
                JME-23-0112
                10.1530/JME-23-0112
                10959011
                38240302
                36c7f906-5947-4b34-b393-4916352701d6
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 06 September 2023
                : 19 January 2024
                Categories
                Thematic Review

                Endocrinology & Diabetes
                incretin,glp-1,gip,enteroendocrine cells,diabetes,obesity
                Endocrinology & Diabetes
                incretin, glp-1, gip, enteroendocrine cells, diabetes, obesity

                Comments

                Comment on this article

                Related Documents Log