Role of the Vagus Nerve in Mediating Proximal Nutrient-Induced Glucagon-Like Peptide-1 Secretion*

Rocca, Antonio S.; Brubaker, Patricia L.

doi:10.1210/endo.140.4.6643

Cited by 357 publications

(185 citation statements)

References 37 publications

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“…Furthermore, lithium may alter the response of the intestinal L cells to known secretagogues, including nutrients, as well as several neuro/endocrine gut hormones (31). We have recently observed a similar synergistic effect of fatty acids on glucose-dependent insulinotropic peptide (71) and of leptin on gastrin-releasing peptide-stimulated GLP-1 secretion (72). These hypotheses deserve further examination in vivo.…”

Section: Discussionmentioning

confidence: 66%

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Ni¹,

Anini²,

Fang³

et al. 2003

Journal of Biological Chemistry

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The proglucagon gene encodes several peptide hormones that regulate blood glucose homeostasis, growth of the small intestine, and satiety. Among them, glucagon-like peptide 1 (GLP-1) lowers blood glucose levels in patients with diabetes and inhibits eating and drinking in fasted rats. Although proglucagon transcription and GLP-1 synthesis were shown to be activated by forskolin and other protein kinase A (PKA) activators, deleting or mutating the cAMP-response element (CRE) only moderately attenuates the proglucagon gene promoter in response to PKA activation. Therefore, PKA may activate proglucagon transcription via a mechanism independent of the CRE motif. Recently, PKA was shown to phosphorylate and inactivate GSK-3␤, a key mediator in the Wnt signaling pathway. We show here that lithium, an inhibitor of GSK-3␤, activates proglucagon gene transcription and stimulates GLP-1 synthesis in an intestinal endocrine L cell line, GLUTag. The activation was also observed in primary fetal rat intestinal cell (FRIC) cultures, but not in a pancreatic A cell line. Co-transfection of ␤-catenin, a downstream effector of GSK-3␤ activities, activated the proglucagon gene promoter without a CRE. Furthermore, forskolin and 8-Br-cAMP phosphorylated GSK-3␤ at serine 9 in intestinal proglucagon-producing cells, and both lithium and forskolin induced the accumulation of free ␤-catenin in these cell lines. These observations indicate that the proglucagon gene is among the targets of the Wnt signaling pathway.

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Section: Discussionmentioning

confidence: 66%

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Ni¹,

Anini²,

Fang³

et al. 2003

Journal of Biological Chemistry

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“…However, the rapid postprandial increase in the plasma concentration of GLP1 generally parallels GIP responses (Knop et al 2007). Both neural and endocrine mechanisms have been proposed to account for this (Plaisancie et al 1994, Rocca & Brubaker 1999, Hansen & Holst 2002, but a simpler explanation has now been provided with the demonstration that proximal L-cells are capable of providing similar responses to nutritional and other stimuli as those elicited from the distal small intestine (Svendsen et al 2015). In addition, there is strong evidence that the small intestinal cells may be more closely related and more promiscuous in terms of secretory products than hitherto believed, showing a high degree of co-expression of several gut hormones , Egerod et al 2012, Sykaras et al 2014.…”

Section: Discussionmentioning

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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“…In addition, taste receptors (primarily T1R2/T1R3 and a-gustducin) in the stomach and intestine seem to regulate the secretion of GLP1 (47,48,49). Paracrine, neuronal and neurohormonal mechanisms may also be important for the facilitation of postprandial GLP1 secretion (50,51,52,53). As mentioned earlier, bile acids are able to activate TGR5 (7, 8, 9), resulting in GLP1 secretion from intestinal L cells (12,14).…”

Section: Glp1 Secretionmentioning

confidence: 94%

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

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Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently -despite elusive mechanisms of action -bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

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Role of the Vagus Nerve in Mediating Proximal Nutrient-Induced Glucagon-Like Peptide-1 Secretion*

Cited by 357 publications

References 37 publications

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

Transcriptional Activation of the Proglucagon Gene by Lithium and β-Catenin in Intestinal Endocrine L Cells

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

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

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