Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx

Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Albrechtsen, Nicolai J. Wewer; Hartmann, Bolette; Holst, Jens J.

doi:10.1152/ajpendo.00012.2015

Cited by 34 publications

(36 citation statements)

References 29 publications

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“…Similarly, total NT and total PYY were measured using in‐house RIA assays, employing C‐terminally targeting antibodies for both peptides, thus measuring both intact (NT 1–13 and PYY 1–36) and cleaved isoforms ((Kuhre et al. ); (Torang et al. )).…”

Section: Methodsmentioning

confidence: 99%

On the relationship between glucose absorption and glucose‐stimulated secretion of GLP ‐1, neurotensin, and PYY from different intestinal segments in the rat

et al. 2017

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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.

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Section: Methodsmentioning

confidence: 99%

On the relationship between glucose absorption and glucose‐stimulated secretion of GLP ‐1, neurotensin, and PYY from different intestinal segments in the rat

et al. 2017

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“…3D97), thus measuring total neurotensin (Kuhre et al. ). TBA concentrations were determined using an enzyme cycling based TBA Assay Kit from Diazyme (Cat No DZ042A‐K, San Diego, CA, USA; intra‐assay coefficient of variation (CV): 3.9%, inter‐assay CV: 2.9%).…”

Section: Methodsmentioning

confidence: 99%

Chenodeoxycholic acid stimulates glucagon‐like peptide‐1 secretion in patients after Roux‐en‐Y gastric bypass

Nielsen

Svane

Kuhre

et al. 2017

Physiological Reports

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Postprandial secretion of glucagon‐like peptide‐1 (GLP‐1) is enhanced after Roux‐en‐Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP‐1 secretion through activation of TGR5‐receptors. We aimed to evaluate GLP‐1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB‐operated participants. Eleven participants (BMI 29.1 ± 1.2, age 37.0 ± 3.2 years, time from RYGB 32.3 ± 1.1 months, weight loss after RYGB 37.0 ± 3.1 kg) were studied in a placebo‐controlled, crossover‐study. On three different days, participants ingested (1) placebo (water), (2) UDCA 750 mg, (3) CDCA 1250 mg (highest recommended doses). Oral intake of CDCA increased plasma concentrations of GLP‐1, C‐peptide, glucagon, peptide YY, neurotensin, total bile acids, and fibroblast growth factor 19 significantly compared with placebo (all P < 0.05 for peak and positive incremental area‐under‐the‐curve (piAUC)). All plasma hormone concentrations were unaffected by UDCA. Neither UDCA nor CDCA changed glucose, cholecystokinin or glucose‐dependent insulinotropic polypeptide (GIP) concentrations. In conclusion, our findings demonstrate that the primary bile acid chenodeoxycholic acid is able to enhance secretion of gut hormones when administered orally in RYGB‐operated patients—even in the absence of nutrients.

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“…Intact, bioactive GIP was measured using in-house RIA (antibody 98171), which reacts with the N-terminal part of intact GIP (1-42), and cross-reacts < 0.1% with GIP (3-42) or the structurally related peptides: GLP-1 (7/9-36) amide, GLP-2 (1-33), or glucagon (Deacon et al 2000). NT was measured using an in-house N-terminal RIA, thus measuring total NT (antibody 3D97) (Kuhre et al 2015). For GLUTag and STC-1, PYY total was measured using a side-viewing antibody (Cat.…”

Section: Biochemical Measurementsmentioning

confidence: 99%

Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: a comparison to native L-cells

Kuhre¹,

Albrechtsen²,

Deacon³

et al. 2016

Journal of Molecular Endocrinology

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ResearchPeptide production in GLP1-producing cell lines r e kuhre and others 56:3 (2016) 56, 201-211 Journal of Molecular Endocrinology 201-211Key Words AbstractGLUTag, NCI-H716, and STC-1 are cell lines that are widely used to study mechanisms underlying secretion of glucagon-like peptide-1 (GLP-1), but the extent to which they resemble native L-cells is unknown. We used validated immunoassays for 14 different hormones to analyze peptide content (lysis samples; n = 9 from different passage numbers) or peptide secretion in response to buffer (baseline), and after stimulation with 50 mM KCl or 10 mM glucose + 10 µM forskolin/3-isobutyl-1-methylxanthine (n = 6 also different passage numbers). All cell lines produced and processed proglucagon into GLP-1, GLP-2, glicentin, and oxyntomodulin in a pattern (prohormone convertase (PC)1/3 dependent) similar to that described for human gut. All three cell lines showed basal secretion of GLP-1 and GLP-2, which increased after stimulation. In contrast to freshly isolated murine L-cells, all cell lines also expressed PC2 and secreted large amounts of pancreatic glucagon. Neurotensin and somatostatin storage was low and secretion was not consistently increased by stimulation. STC-1 cells released more glucose-dependent insulinotropic polypeptide than GLP-1 at baseline (P < 0.01) and KCl elevated its secretion (P < 0.05). Peptide YY, which normally co-localizes with GLP-1 in distal L-cells, was not detected in any of the cell lines. GLUTag and STC-1 cells also expressed vasoactive intestinal peptide, but none expressed pancreatic polypeptide or insulin. GLUTag contained and secreted large amounts of CCK, while NCI-H716 did not store this peptide and STC-1 contained low amounts. Our results show that hormone production in cell line models of the L-cell has limited similarity to the natural L-cells.

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Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx

Cited by 34 publications

References 29 publications

On the relationship between glucose absorption and glucose‐stimulated secretion of GLP ‐1, neurotensin, and PYY from different intestinal segments in the rat

On the relationship between glucose absorption and glucose‐stimulated secretion of GLP ‐1, neurotensin, and PYY from different intestinal segments in the rat

Chenodeoxycholic acid stimulates glucagon‐like peptide‐1 secretion in patients after Roux‐en‐Y gastric bypass

Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: a comparison to native L-cells

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