Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line

Simpson, Anna K.; Ward, Patrick S.; Wong, Kai Yuen; Collord, Grace; Habib, Abdella M.; Reimann, Frank; Gribble, Fiona M.

doi:10.1007/s00125-007-0750-9

Cited by 79 publications

(88 citation statements)

References 38 publications

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“…Activation of GPR119 by oleoylglycerol, or of GPBAR1 by bile acids, could potentially trigger elevation of the cAMP concentration in enteroendocrine cells, enhancing hormone secretion by a mechanism distinct from either the depolarising effect of glucose or Gq-coupled response to FFAR1 and GPR120 activation. Rising cAMP levels in enteroendocrine cells have been linked to cytosolic Ca 2 + elevation, enhanced rates of secretion and increased gene transcription, via pathways including the recruitment of protein kinase A and Epac2 (54,(62)(63)(64) .…”

Section: Lipid Sensingmentioning

confidence: 99%

The gut endocrine system as a coordinator of postprandial nutrient homoeostasis

Gribble¹

2012

Proc. Nutr. Soc.

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Hormones from the gastrointestinal (GI) tract are released following food ingestion and trigger a range of physiological responses including the coordination of appetite and glucose homoeostasis. The aim of this review is to discuss the pathways by which food ingestion triggers secretion of cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and the altered patterns of gut hormone release observed following gastric bypass surgery. Our understanding of how ingested nutrients trigger secretion of these gut hormones has increased dramatically, as a result of physiological studies in human subjects and animal models and in vitro studies on cell lines and primary intestinal cultures. Specialised enteroendocrine cells located within the gut epithelium are capable of directly detecting a range of nutrient stimuli through a range of receptors and transporters. It is concluded that the arrival of nutrients at the apical surface of enteroendocrine cells is a major stimulus for gut hormone release, thereby coupling these endocrine signals to the arrival of absorbed nutrients in the bloodstream.Glucagon-like peptide-1: Cholecystokinin: Glucose-dependent insulinotropic polypeptide:Enteroendocrine: Diabetes: Obesity Physiological responses to food ingestion include the regulation of appetite and glucose homoeostasis as well as the control of gastric motility and secretion. Although rising circulating nutrient concentrations act as a sign of recent food intake, however, they do not indicate whether the nutrients are of alimentary origin and therefore do not convey sufficient information to enable the body to handle them appropriately. This role is fulfilled by neurohormonal signals from the gut, which indicate the volume and content of ingested food. A number of enteric peptides have been implicated in signalling from the gut to the brain and the pancreas. These include cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and peptide YY (PYY), which target receptors in the pancreas and enteric and central nervous systems. Interest in gut peptides has increased in recent decades, with the finding that they have profound and sustained physiological effects on appetite and insulin release (1)(2)(3)(4) . GLP-1, an incretin hormone that stimulates insulin release and reduces food intake, has been very successfully exploited for the treatment of type-2 diabetes. Injectable GLP-1 mimetics and orally available inhibitors of GLP-1 degradation (DPP4 inhibitors) are now widely prescribed and match the effectiveness of other oral therapies on glycaemic control, but are additionally weight-lowering, or at least weight-neutral, and are associated with a low incidence of hypoglycaemic side effects (5) . Recent excitement in the gut peptide field has been triggered by the results of using gastric bypass surgery as a treatment for morbid obesity. Somewhat unexpectedly, it was observed that a number of bariatric procedures have effec...

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Section: Lipid Sensingmentioning

confidence: 99%

The gut endocrine system as a coordinator of postprandial nutrient homoeostasis

Gribble¹

2012

Proc. Nutr. Soc.

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“…Previous studies employing several experimental models including single K-and L-cells have shown that the hormones are secreted in response, for example, to glucose, which after entry via the sodium-glucose transporter-1 results in membrane depolarization and exocytosis secondary to calcium influx in both cell types (Reimann et al 2008, Parker et al 2009. Other studies have shown that stimuli activating the cAMP system may also result in both GLP1 and GIP secretion (Simpson et al 2007, Moss et al 2012, Hauge et al 2014, Svendsen et al 2015.…”

Section: Introductionmentioning

confidence: 99%

GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness

Svendsen¹,

Pais²,

Engelstoft³

et al. 2015

Journal of Endocrinology

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The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from intestinal endocrine cells, the so-called L-and K-cells. The cells are derived from a common precursor and are highly related, and co-expression of the two hormones in so-called L/K-cells has been reported. To investigate the relationship between the GLP1-and GIP-producing cells more closely, we generated a transgenic mouse model expressing a fluorescent marker in GIP-positive cells. In combination with a mouse strain with fluorescent GLP1 cells, we were able to estimate the overlap between the two cell types. Furthermore, we used primary cultured intestinal cells and isolated perfused mouse intestine to measure the secretion of GIP and GLP1 in response to different stimuli. Overlapping GLP1 and GIP cells were rare (w5%). KCl, glucose and forskolinCIBMX increased the secretion of both GLP1 and GIP, whereas bombesin/ neuromedin C only stimulated GLP1 secretion. Expression analysis showed high expression of the bombesin 2 receptor in GLP1 positive cells, but no expression in GIP-positive cells. These data indicate both expressional and functional differences between the GLP1-producing 'L-cell' and the GIP-producing 'K-cell'.

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“…When GIP-producing K cells in the duodenum were engineered to produce insulin under the control of the GIP gene promoter, they functioned in place of beta cells to maintain whole-body glucose homeostasis [5,7]. In vitro data from immortalised L cell lines suggest that GLP-1 release from L cells and insulin release from beta cells share some common glucose-sensing machinery including glucokinase [8,9]. In addition to glucokinaseregulated enteroendocrine cells releasing GIP and GLP-1, glucose-responsive neurons in the myenteric plexus may also be regulated by glucokinase [1,10,11].…”

Section: Introductionmentioning

confidence: 99%

Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor

et al. 2008

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Aims/hypothesis The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. Methods We compared GLP-1 and GIP concentrations measured at five time-points during a 75 g OGTT in 49 participants having GCK mutations with those of 28 familial controls. Mathematical modelling of glucose, insulin and C-peptide was used to estimate basal insulin secretion rate (BSR), total insulin secretion (TIS), beta cell glucose sensitivity, potentiation factor and insulin secretion rate (ISR).Results GIP and GLP-1 profiles during the OGTT were similar in GCK mutation carriers and controls (p=0.52 and p=0.44, respectively). Modelled variables of beta cell function showed a reduction in beta cell glucose sensitivity (87 pmol min Conclusions/interpretation Glucokinase, the major pancreatic glucose sensor, is not the main gut glucose sensor. By modelling OGTT data in GCK mutation carriers we were able to distinguish a specific beta cell glucose-sensing defect. Our data suggest a reduction in potentiation of insulin secretion by glucose that is independent of differences in incretin hormone release.

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Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line

Cited by 79 publications

References 38 publications

The gut endocrine system as a coordinator of postprandial nutrient homoeostasis

The gut endocrine system as a coordinator of postprandial nutrient homoeostasis

GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness

Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor

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