Abstract
Ingested glucose powerfully stimulates the secretion of appetite‐ and metabolism‐regulating peptide hormones from the gut – including glucagon‐like peptide‐1 (GLP‐1), neurotensin (NT), and polypeptide YY (PYY). However, the regional origin of these secretions after glucose stimulation is not well characterized, and it remains uncertain how their secretion is related to glucose absorption. We isolated and perfused either the upper (USI) or the lower (LSI) small intestine or the colon from rats and investigated concomitant glucose absorption and secretory profiles of GLP‐1, NT, and PYY. In the USI and LSI luminal glucose (20%, w/v) increased GLP‐1 and NT secretion five to eightfold compared to basal secretion. Compared to the USI, basal and stimulated GLP‐1 secretion from the colon was 8–10 times lower and no NT secretion was detected. Luminal glucose stimulated secretion of PYY four to fivefold from the LSI and from the USI and colon, but the responses in the USI and colon were 5‐ to 15‐fold lower than in the LSI. Glucose was absorbed to a comparable extent in the USI and LSI by mechanisms that partly depended on both SGLT1 and GLUT2 activity, whereas the absorption in the colon was 80–90% lower. The absorption rates were, however, similar when adjusted for segmental length. Glucose absorption rates and NT, PYY and in particular GLP‐1 secretion were strongly correlated (P < 0.05). Our results indicate that the rate of secretion of GLP‐1, NT, and PYY in response to glucose, regardless of the involved molecular machinery, is predominantly regulated by the rate of glucose absorption.
Highlights
The gut peptide hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) play an important role in the regulation of appetite and food intake (Baggio and Drucker 2007; Steinert et al 2017; Tan et al 2017), and neurotensin secreted from intestinal N-cells may inhibit appetite (Levine et al 1983)
Several studies have addressed the molecular mechanisms underlying the secretion of the appetite- and metabolismregulating hormones, GLP-1, NT, and PYY during the last decade, as recently reviewed (Gribble and Reimann 2016; Husted et al 2017), but less attention has been devoted to analysis of the segments of the gut from where these hormones are secreted in response to different secretagouges
The expression levels of different molecular sensors in intestinal epithelium of mice and humans vary along the intestine (Symonds et al 2015) and this may result in different regional responses of GLP-1, NT, and PYY to different stimuli
Summary
The gut peptide hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) play an important role in the regulation of appetite and food intake (Baggio and Drucker 2007; Steinert et al 2017; Tan et al 2017), and neurotensin secreted from intestinal N-cells may inhibit appetite (Levine et al 1983). Recent studies in people with gastric bypass surgery indicate that the exaggerated increase in GLP-1, NT, and PYY secretion after oral glucose intake is related to the rate of glucose absorption rather than the presence of glucose in the gut (Jørgensen et al 2012; Jacobsen et al 2013), and this assumption is supported by in vitro experiments (Parker et al 2012; Kuhre et al 2014a, 2014b) This apparently important relationship has not, to our knowledge, been studied directly in a quantitative manner. All the important physiological parameters such as cell polarization, contact with normal neighbor cells, nutrition, and respiration and most importantly for studies of transmucosal transport: perfusion flow (and convective drag of absorbed nutrients) are preserved (Svendsen and Holst 2016), allowing studies of the full dynamics of absorption and secretion
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