Hormones from the gut are central to the control of appetite and insulin release. Drugs based on the gut hormone glucagon-like peptide-1 (GLP-1) have proved highly successful for treating type 2 diabetes, and also suppress food intake. In collaboration with Frank Reimann our group researches how gut hormones are released and their actions on target tissues. We hope this will lead to the development of new drugs or diets that treat diabetes and obesity by targeting gut hormone release.
Secretion and action of gut hormones
We use optical and electrophysiological recording techniques to monitor stimulus detection and vesicle release from primary and immortalized GLP-1-secreting cells. To identify living gut endocrine cells, we have generated transgenic models in which hormone producing cells, or cellular targets of gut hormones, are labelled by cell-specific fluorescent markers and reporters of cytoplasmic signalling pathways. The mechanisms by which cells detect stimuli are identified by combining methods such as live cell imaging, electrophysiology, transcriptomics and assays of hormone secretion.
Gut hormone release in humans
The release of gut hormones after a meal conveys signals to the brain to stop eating, to the pancreas to produce insulin and to the gut to coordinate digestion. We are interested in establishing how gut hormones are released in man, their impact on whole body metabolism and their contributions to side effects after bypass surgery.
Our ongoing research projects include:
- Understanding how gut hormones contribute to the metabolic changes and symptoms observed after gastrectomy
If you might be interested in participating in research studies on gut hormones, please send your contact details to email@example.com.
Adriaenssens AE, Svendsen B, Lam BY, Yeo GS, Holst JJ, Reimann F, Gribble FM. Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. Diabetologia. 2016; 59:2156-65 PMID: 27390011
Pais R, Rievaj J, Larraufie P, Gribble F, Reimann F. Angiotensin II type 1 receptor dependent GLP-1 and PYY secretion in mice and humans. Endocrinology. 2016 157:3821-3831 PMID: 27447725
Meek CL, Lewis HB, Vergese B, Park A, Reimann F, Gribble F. The effect of encapsulated glutamine on gut peptide secretion in human volunteers. Peptides. 2016 Mar;77:38-46 PMID: 26541888
Brighton CA, Rievaj J, Kuhre RE, Glass LL, Schoonjans K, Holst JJ, Gribble FM, Reimann F. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors. Endocrinology. 2015 Nov;156(11):3961-70 PMID: 26280129
Adriaenssens A, Lam BY, Billing L, Skeffington K, Sewing S, Reimann F, Gribble F. A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium. Endocrinology. 2015 Nov;156(11):3924-36 PMID: 26241122
Richards P, Pais R, Habib AM, Brighton CA, Yeo GS, Reimann F, Gribble FM. High fat diet impairs the function of glucagon-like peptide-1 producing L-cells. Peptides. 2016 Mar;77:21-7 PMID: 26145551
Grosse J, Heffron H, Burling K, Hossain MA, Habib AM, Rogers GJ, Richards P, Larder R, Rimmington D, Adriaenssens AE, Parton L, Powell J, Binda M, Colledge WH, Doran J, Toyoda Y, Wade JD, Aparicio S, Carlton M, Coll AP, Reimann F, O’Rahilly S, Gribble FM. Insulin-like peptide 5 is an orexigenic gastro-intestinal hormone. Proc Natl Acad Sci U S A 2014:111:11133-8 PMID: 25028498
Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC, Trapp S, Gribble FM, Reimann F. Identification and characterisation of glucagon-like peptide-1 receptor expressing cells using a new transgenic mouse model. Diabetes. 2014; 63:1224-33 PMID: 24296712
Habib AM, Richards P, Rogers GJ, Reimann F, Gribble FM. Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells. Diabetologia. 2013; 56:1413-6 PMID: 23519462
Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CA, Parker HE, Morley TC, Yeo GS, Reimann F, Gribble FM. Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology. 2012; 153:3054-65 PMID: 22685263
Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2. Diabetes. 2012; 61:364-71. PMID: 2219064
Greenfield FR, Farooqi IS, Keogh J, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM. Oral glutamine increases circulating GLP-1, glucagon and insulin levels in lean, obese and type 2 diabetic subjects. Am J Clin Nutr. 2009; 89:106-13. PMID: 19056578
Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM. Glucose-sensing in L-cells: a primary cell study. Cell Metab. 2008; 8:532-539. PMID: 19041768
Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006; 444: 894-898. PMID: 17167479