Lymph, Pancreatic and Gastrointestinal Hormones in Response to Feeding in the Conscious Pig

Manolas, Konstantinos J; Adrian, Thomas E.; Dunlop, H.M.; Bacarese-Hamilton, A.J.; Bloom, S.R.; Welbourn, Richard

doi:10.1159/000128485

Cited by 6 publications

(9 citation statements)

References 17 publications

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“…The significantly different lymph/plasma hormone levels of PYY and GLP-1 suggest that the extraordinarily high lymph concentrations of GLP-1 are not due simply to a concentration effect caused by the smaller pool size and slower turnover of lymph (10,26). This conclusion is consistent with the previous report of lower gut hormone concentrations in canine lymph compared with plasma (19). Rather, it seems likely that the higher lymph concentrations of GLP-1 indicate targeted secretion of peptide in the intestinal lymphatic system.…”

Section: Discussionsupporting

confidence: 91%

“…The fenestrated capillary network of the intestinal villus is much nearer the basal aspect of the mucosal cells than the initial lacteals (2), and so is the first space exposed to substances absorbed or secreted by the mucosa. In the only previous report of gastrointestinal hormones from intestinal lymphatics, concentrations of gastrin, neurotensin, vasoactive intestinal peptide, substance P, and bombesin were ϳ50% those of plasma in a dog model (19), consistent with primary clearance of peptides released from mucosal cells or enteric neurons by blood capillaries. The case for GLP-1 seems to be much different in that the greatly elevated lymph, compared with portal plasma, levels suggest a different means of distribution in the vasculature draining the villus.…”

Section: Discussionsupporting

confidence: 53%

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Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system

D’Alessio

Sun

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Glucagon like peptide 1 (GLP-1) is an intestinal hormone that plays an important role in glucose metabolism. GLP-1 is released from mucosal L cells following nutrient ingestion and contributes to the incretin effect, with the enhancement of insulin secretion occurring with enteral compared with intravenous glucose administration. The mechanisms linking nutrient absorption and GLP-1 secretion are unknown, and studies addressing this topic, particularly in small animal models, have been hampered by the relatively low concentrations of GLP-1 in the circulation. We hypothesized that GLP-1 levels would be higher in samples of intestinal lymph compared with plasma and could provide a novel system in which to study meal-induced hormone secretion. We addressed this hypothesis in conscious rats with indwelling catheters in the portal vein and distal intestinal lymph duct. These animals had plasma and lymph sampled before and for 240 min after instillation of a liquid meal in the gastrointestinal tract. Lymph contained detectable concentrations of glucose, insulin, and GLP-1 that were reliably measured using our assays. Before and after the Ensure feeding, plasma insulin levels were approximately two times as high in portal plasma as intestinal lymph. In marked contrast, GLP-1 levels were five to six times higher in lymph relative to portal plasma following nutrient administration. This relative difference in GLP-1 levels was even greater when lymph was compared with peripheral plasma and dramatically exceeded the ratio of lymph to plasma peptide tyrosine-tyrosine concentrations. This is the first observation of a gastrointestinal hormone being disproportionately transported in lymph. The remarkable levels of GLP-1 in intestinal lymph demonstrate the potential for lymphatic sampling as a more sensitive means of studying the secretory physiology of this hormone in vivo. In addition, these data raise the possibility that intestinal lymph may serve as a specialized signaling conduit for regulatory peptides secreted by gastrointestinal endocrine cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 53%

Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system

D’Alessio

Sun

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Other investigators have observed that gastrin levels are significantly increased at 20-30 min and 2 h postprandially in growing or adult pigs and dogs (19,22). We did not observe significant increases above baseline concentrations following CF; however, piglets fed HOF demonstrated significant postprandial increases 15 and 30 min following a meal.…”

Section: Resultscontrasting

confidence: 77%

“…In this study we evaluated the effects of gastrin, secretin, CCK, and motilin. Compared to the 20-h fasting period reported in growing pigs (19), we obtained baseline hormone levels in neonatal piglets following a 17-h fast. We judged this to be a sufficient period based on the gastric emptying time of neonatal piglets (20).…”

Section: Resultsmentioning

confidence: 99%

Hyperosmolal Formula in Neonatal Piglets

Szabo,

Rayford,

Uthman

et al. 1990

J. pediatr. gastroenterol. nutr.

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SummaryIngestion of hyperosmolal formula (HOF) by neonatal piglets has been shown to cause significant time‐dependent reduction in phase 3 myoclectric activity, which persists in the terminal ileum. To determine whether a single hyperosmolal meal leads to elevated concentrations of gastrointestinal (GI) hormones that inhibit intestinal motility and/or promote bacterial proliferation and disruption of intestinal mucosa, we studied 20 healthy neonatal piglets following feeding with an increased HOF (872 ± 32 mOsmol/kg, n = 10) and commercial pig milk formula (481 ± 41 mOsmol/kg, n = 10). Gastrin, secretin, cholecystokinin, and motilin concentrations were determined by radioimmunoassay during fasting and postprandial periods (15, 30, 45, 120, 180, and 240 min). Gastrin concentrations were significantly increased at 15 and 30 min following a hyperosmolal meal (p < 0.01), but there were no statistical differences in GI hormone concentrations between groups. These transient elevations of gastrin concentrations are associated with significant postprandial reductions in phase 3 small intestinal myoelectric activity (SIMEA) that we have observed. Aerobic bacterial titers were not significantly different between proximal and distal small intestinal segments or between experimental groups, and anaerobic bacteria were seldom recovered. Thus, SIMEA was not sufficiently altered to produce significant bacterial proliferation. Small intestinal histology, assessed by light microscopy, showed normal proximal and distal small intestinal mucosa in 8 of 10 piglets from each group. Therefore, orogastric instillation of a single hyperosmolal feed does not result in intestinal mucosal damage. Further studies are warranted to determine the effects of hyperosmolal feeds when additional risk factors exist in the neonate.

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“…This architecture is compatible with the 50% lower levels of gastrin, vasoactive intestinal peptide, neurotensin, substance P, and bombesin in lymph than in plasma (28). However, we have recently reported that GLP-1 was six times higher in lymph than in plasma (7), raising the question as to whether some peptides are selectively targeted to lymph.…”

Section: Discussionsupporting

confidence: 72%

The intestinal lymph fistula model—a novel approach to study ghrelin secretion

Tong

Tschöp

Aulinger

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling this compartment would provide advantages for studying ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the jugular vein and mesenteric lymph duct before and after intraduodenal (ID) administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher than in plasma (means +/- SE: 3,307.9 +/- 272.9 vs. 2,127.1 +/- 115.0 pg/ml, P = 0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and plasma (0.91 +/- 0.28 vs. 1.20 +/- 0.36, P = 0.76). The principle enzymes responsible for deacylation of ghrelin were lower in lymph than in plasma. Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph compared with at 1 h in plasma. The return of suppressed ghrelin levels to baseline was also delayed in lymph. Similarly, dextrin also induced significant suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not (P = 0.32). On the basis of these findings, it appears that intestinal lymph, which includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin. Despite reduced deacylating activity in lymph, there is not a disproportionate amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are slower in lymph than plasma, but the magnitude of change is greater. Assessing ghrelin levels in the lymph may be advantageous for studying its secretion and concentrations in the gastric mucosa.

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Lymph, Pancreatic and Gastrointestinal Hormones in Response to Feeding in the Conscious Pig

Cited by 6 publications

References 17 publications

Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system

Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system

Hyperosmolal Formula in Neonatal Piglets

The intestinal lymph fistula model—a novel approach to study ghrelin secretion

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