Important species differences regarding lymph contribution to gut hormone responses

Hansen, Melissa Voigt; Hjøllund, Karina Rahr; Hartmann, Bolette; Plamboeck, Astrid; Deacon, Carolyn F.; Albrechtsen, Nicolai J. Wewer; Holst, Jens J.

doi:10.1016/j.peptides.2015.05.008

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…Nor have the results of tests of meal-related hormone changes in the lymph been straightforward. For example, post-meal concentrations of GLP-1 were reported to be ϳ6-fold higher in lymph than in hepatic portal-vein plasma in rats (178) and ϳ8-fold higher in lymph than in orbital-plexus plasma in mice ( 553), but ϳ10-fold lower in lymph in hepatic portal-vein plasma in swine (308).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin, CCK, GLP-1, and PYY(3–36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB

Steinert

Feinle‐Bisset

Asarian

et al. 2017

Physiological Reviews

460

415

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The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

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Section: Discussionmentioning

confidence: 99%

Ghrelin, CCK, GLP-1, and PYY(3–36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB

Steinert

Feinle‐Bisset

Asarian

et al. 2017

Physiological Reviews

460

415

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“…It has been speculated that the lymph drainage of the intestine might serve as a route for delivery of GLP‐1 to the circulation (Lu et al, 2012), but the lymph flow is very limited; there may be species differences, and the amounts delivered to the blood stream are probably very small (Hansen et al, 2015; Jejelava et al, 2018).…”

Section: Biosynthesis Processing and Secretion Of Glp‐1mentioning

confidence: 99%

“…In further support of these observations, the suppressive effects of intraperitoneal injections of GLP‐1 on food intake and blood glucose levels were attenuated by complete sub‐diaphragmatic vagal de‐afferentation in rats (Hayes et al, 2011), indicating that these systemic effects are mediated in part through activation of GLP‐1 receptors on the vagal afferent nerve terminals. In accordance, intraperitoneal administration of 125 I‐exendin (Billeschou et al, 2021; Billing et al, 2018, 2019; Billings et al, 2018; Brookes et al, 2013; Brubaker, 2018; Bucinskaite et al, 2009; Buckley et al, 2019; Buhl et al, 1988; Canfora et al, 2017; Chen et al, 2017; Christiansen et al, 2018; Christiansen et al, 2019; Daniel et al, 2002; Day et al, 2009; de Heer et al, 2007; Deacon et al, 1995; Drucker & Yusta, 2014; Eissele et al, 1990, 1992; Fehmann et al, 1995; Friis‐Hansen et al, 2001; Gabery et al, 2020; Gasbjerg et al, 2019; Glass et al, 2017; Gouyer et al, 2010; Hanby et al, 1999; Hansen et al, 1999, 2015; Hayes et al, 2011) resulted in labelling of myenteric ganglia of the distal ileum, thus supporting the interpretation of experiments involving intraperitoneal administration of GLP‐1 to reflect interactions with nerve fibres within the myenteric plexus (Hayes et al, 2011).…”

Section: Functional Significance Of Gi Expression Of the Receptormentioning

confidence: 99%

“…The nature of the GLP‐1 receptor‐positive fibres in the intestinal wall is not clear. The strongest antibody staining for GLP‐1 receptors and the greatest accumulation of 125 I‐exendin (Billeschou et al, 2021; Billing et al, 2018, 2019; Billings et al, 2018; Brookes et al, 2013; Brubaker, 2018; Bucinskaite et al, 2009; Buckley et al, 2019; Buhl et al, 1988; Canfora et al, 2017; Chen et al, 2017; Christiansen et al, 2018, 2019; Daniel et al, 2002; Day et al, 2009; de Heer et al, 2007; Deacon et al, 1995; Drucker & Yusta, 2014; Eissele et al, 1990, 1992; Fehmann et al, 1995; Friis‐Hansen et al, 2001; Gabery et al, 2020; Gasbjerg et al, 2019; Glass et al, 2017; Gouyer et al, 2010; Hanby et al, 1999; Hansen et al, 1999, 2015; Hayes et al, 2011) grains were observed in and around myenteric plexuses located in the distal intestine, namely, in the distal ileum and in the proximal and distal large intestine. Myenteric ganglia of the duodenum, jejunum and gastric pylorus also displayed staining for GLP‐1 receptors, whereas the nerve fibres in the gastric corpus and caecum were very weakly stained.…”

Section: Functional Significance Of Gi Expression Of the Receptormentioning

confidence: 99%

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Actions of glucagon‐like peptide‐1 receptor ligands in the gut

Holst

Andersen

Grunddal

2021

British J Pharmacology

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The incretin hormone glucagon‐like peptide‐1 (GLP‐1) is inactivated by the enzyme dipeptidyl peptidase‐4 even before it leaves the gut, but it seems to act predominantly via activation of intestinal sensory neurons expressing GLP‐1 receptors. Thus, activation of vagal afferents is probably responsible for its effects on appetite and food intake, gastrointestinal secretion and motility, and pancreatic endocrine secretion. However, GLP‐1 receptors are widely expressed in the gastrointestinal (GI) tract, including epithelial cells in the stomach, and the Brunner glands, in endocrine cells of the gut epithelium, and on mucosal lymphocytes. In this way, GLP‐1 may have important local actions of epithelial protection and endocrine signalling and may interact with the immune system. We review the formation and release of GLP‐1 from the endocrine L cells and its fate after release and describe the localization of its receptor throughout the GI tract and discuss its direct or indirect actions in the GI tract. LINKED ARTICLES This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc

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Physiology of the Incretin Hormones,GIPandGLP‐1—Regulation of Release and Posttranslational Modifications

Holst

Albrechtsen

Deacon

2019

Comprehensive Physiology

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The focus of this article is on the analysis of the release and postrelease fate of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Their actions are dealt with to the extent that they are linked to their secretion. For both hormones, their posttranslational processing is analyzed in detail, because of its importance for the understanding of the molecular heterogeneity of the hormones. Methods of analysis, in particular regarding measurements in plasma from in vivo experiments, are discussed in detail in relation to the molecular heterogeneity of the hormones, and the importance of the designations "total" versus "intact hormones" is explained. Both hormones are substrates for the ubiquitous enzyme, dipeptidyl peptidase-4, which inactivates the peptides with dramatic consequences for their physiological spectrum of activities. The role of endogenous and exogenous antagonists of the receptors is discussed in detail because of their importance for the elucidation of the physiology and pathophysiology of the hormones. Regarding the actual secretion, the most important factors are discussed, including gastric emptying rate and the influence of the different macronutrients. Additional factors discussed are the role of bile, paracrine regulation, the role of the microbiota, pharmaceuticals, and exercise. Finally, the secretion during pathological conditions is discussed.

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Important species differences regarding lymph contribution to gut hormone responses

Cited by 5 publications

References 21 publications

Ghrelin, CCK, GLP-1, and PYY(3–36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB

Ghrelin, CCK, GLP-1, and PYY(3–36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB

Actions of glucagon‐like peptide‐1 receptor ligands in the gut

Physiology of the Incretin Hormones,GIPandGLP‐1—Regulation of Release and Posttranslational Modifications

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