The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas

Heer, Jocelyn de; Pedersen, Jens; Ørskov, Cathrine; Holst, Jens J.

doi:10.1007/s00125-007-0761-6

Cited by 52 publications

(44 citation statements)

References 40 publications

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“…Both GLP-1 and GLP-2 are secreted at equimolar amounts from entero-endocrine L-cells (45), but because of its slower degradation, circulating GLP-2 levels exceed those of GLP-1 by severalfold (46,47). It is therefore likely that the potent glucagonotropic actions of GLP-2 shown previously by our group have supervened the glucagonostatic actions of GLP-1 (44,48). Thus, under physiological conditions, the GLP-1-induced suppression of glucagon secretion might be outweighed by the glucagonotropic actions of GLP-2.…”

Section: Glp-1 Response In Type 2 Diabetesmentioning

confidence: 76%

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

et al. 2008

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OBJECTIVE-Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2) Which endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses?RESEARCH DESIGN AND METHODS-Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined.RESULTS-GIP and GLP-1 levels increased significantly in both experiments (P Ͻ 0.0001). In patients with type 2 diabetes, the initial GIP response was exaggerated compared with control subjects after mixed meal (P Ͻ 0.001) but not after oral glucose ingestion (P ϭ 0.98). GLP-1 levels were similar in all three groups in both experiments. GIP responses were 186 Ϯ 17% higher after mixed meal ingestion than after the oral glucose load (P Ͻ 0.0001), whereas GLP-1 levels were similar in both experiments. There was a strong negative association between fasting glucagon and integrated FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and integrated glucagon levels after glucose or meal ingestion and female sex were positively related to GLP-1 concentrations. Incretin levels were unrelated to measures of glucose control or insulin secretion.CONCLUSIONS-Deteriorations in glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1 levels. This suggests that the defects in GLP-1 concentrations previously described in patients with long-standing type 2 diabetes are likely secondary to other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP-1 concentrations appear to be regulated by different factors and are independent of each other. Diabetes 57:678-687, 2008 P ostprandial glucose homeostasis is controlled not only by the direct stimulation of insulin release by the absorbed nutrients but also through the secretion of incretin hormones, namely gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 (GLP-1) (1-4). In healthy, nondiabetic subjects, the quantitative contribution of this incretin effect to the overall postprandial insulin secretion has been estimated to be 50 -70% (5,6), depending on meal size and composition. In contrast, a marked reduction of the incretin effect is characteristic of patients with type 2 diabetes (7), thereby contributing to the excess postprandial glucose excursions in such patients. Although the exact mechanisms underlying the loss of incretin activity in patients with type 2 diabetes are still not completely understood, two d...

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Section: Glp-1 Response In Type 2 Diabetesmentioning

confidence: 76%

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

et al. 2008

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“…infusion of the peptide has been demonstrated to increase glucagon secretion in healthy, non-obese human subjects both in physiological and pharmacological plasma concentration (Sørensen et al 2003, Meier et al 2006 or in diabetic patients (Christensen et al 2010, Lund et al 2011. GLP2R has been localized to α-cells in both human and rat islets by means of immunohistochemistry as well as real-time PCR (de Heer et al 2007). In contrast, full-length Glp2r mRNA transcripts have not been detected in RNA from murine islets, and GLP2 does not increase plasma glucagon levels in mice (Yusta et al 2000, Bahrami et al 2010.…”

Section: Glp2 and Glycaemic Controlmentioning

confidence: 99%

“…Indeed, a direct action on β-cell function is improbable because the Glp2r mRNA transcripts have not been detected in pancreatic islets, but only in mouse whole pancreas (Bahrami et al 2010) or rat and human pancreatic α-cells (de Heer et al 2007). Despite exogenous GLP2 increases glucagon secretion (Meier et al 2006, de Heer et al 2007, elimination of GLP2R signalling in genetically obese mice leads to increased glucagon secretion and α-cell mass, which has been interpreted as due to increased proinflammatory signals (Bahrami et al 2010), for example interleukin-6, in turn, involved in α-cell mass expansion (Ellingsgaard et al 2008). Unluckily, glucagon levels were not measured in HFD-fed mice after GLP2 (3-33) or Gly 2 -GLP2 chronic treatment.…”

Section: Mechanistic Insightmentioning

confidence: 99%

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Amato¹,

Baldassano²,

Mulè³

2016

Journal of Endocrinology

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Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by intestinal enteroendocrine L-cells and by a discrete population of neurons in the brainstem, which projects mainly to the hypothalamus. The main biological actions of GLP2 are related to the regulation of energy absorption and maintenance of mucosal morphology, function and integrity of the intestine; however, recent experimental data suggest that GLP2 exerts beneficial effects on glucose metabolism, especially in conditions related to increased uptake of energy, such as obesity, at least in the animal model. Indeed, mice lacking GLP2 receptor selectively in hypothalamic neurons that express proopiomelanocortin show impaired postprandial glucose tolerance and hepatic insulin resistance (by increased gluconeogenesis). Moreover, GLP2 acts as a beneficial factor for glucose metabolism in mice with high-fat diet-induced obesity. Thus, the aim of this review is to update and summarize current knowledge about the role of GLP2 in the control of glucose homeostasis and to discuss how this molecule could exert protective effects against the onset of related obesity type 2 diabetes.

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“…Whether or not that may play a role in neoplastic development following exogenous GLP-2 administration remains unanswered (46). Also, extraintestinal expression of GLP-2R has been reported notably in central nervous system, lung, and pancreas in rodents and humans (6,27,50). At the cellular level, GLP-2R is expressed in the enteroendocrine L cells, in intestinal subepithelial myofibroblasts, in enteric neurons of the submucosal and myenteric plexus, in pancreatic alpha cells, and in astrocytes in brain (6,15,27,48).…”

mentioning

confidence: 99%

Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration

El-Jamal

Erdual

Neunlist

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.

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The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas

Cited by 52 publications

References 40 publications

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration

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