Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation

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Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation. / Kuhre, Rune Ehrenreich; Frost, Charlotte Rasmussen; Svendsen, Berit; Holst, Jens Juul.

In: Diabetes, Vol. 63, No. suppl 1, Abstract no 1915-P, 06.2014, p. A491.

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Harvard

Kuhre, RE, Frost, CR, Svendsen, B & Holst, JJ 2014, 'Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation', Diabetes, vol. 63, no. suppl 1, Abstract no 1915-P, pp. A491. https://doi.org/10.2337/db14-1741-2092

APA

Kuhre, R. E., Frost, C. R., Svendsen, B., & Holst, J. J. (2014). Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation. Diabetes, 63(suppl 1), A491. [Abstract no 1915-P]. https://doi.org/10.2337/db14-1741-2092

Vancouver

Kuhre RE, Frost CR, Svendsen B, Holst JJ. Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation. Diabetes. 2014 Jun;63(suppl 1):A491. Abstract no 1915-P. https://doi.org/10.2337/db14-1741-2092

Author

Kuhre, Rune Ehrenreich ; Frost, Charlotte Rasmussen ; Svendsen, Berit ; Holst, Jens Juul. / Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation. In: Diabetes. 2014 ; Vol. 63, No. suppl 1. pp. A491.

Bibtex

@article{1177c7ed8e7e455bac156febb759bb3c,
title = "Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation",
abstract = "We characterized the mechanisms of glucose-stimulated glucagon-like peptide-1 (GLP-1) secretion from isolated rat small intestine perfused at constant rate. Luminal glucose (5 and 20 {\%} (w/v)) stimulated secretion dose dependently (ΔGLP-15{\%} (w/v): 4.77 ± 0.8 vs. GLP-120{\%} (w/v): 18.5 ± 2.8 pM, P<0.0001, n = 6) at rates correlating with glucose absorption (R2: 5{\%} (w/v) = 0.68,R2: 20{\%} (w/v) = 0.87, P < 0.001, n = 6), independent of the osmotic load. Vascular glucose stimulated secretion at 15 mM (21.7 ± 0.5 vs. 25.2 ± 0.6 pmol/l, P < 0.001, n = 6), but not at 5 and 10 mM (P > 0.05). Luminal glucose activated voltage-gated calcium channels in the L-cells, as inhibition with nifedipine (NI; 10 μM) or hyperpolarization with diazoxide completely abolished secretory responses (Glu. 9.19 ± 0.6 vs. 25.1 ± 0.56 pM, P < 0.01, Glu.+NI: 7.90 ± 0.56 vs. 10.57 ± 1.92 pM, P > 0.05, n = 6) (Glu.: 12.0 ± 0.6 vs. 31.8 ± 1.9 pM, P < 0.05, Glu. + DZ: 20.1 ± 1.0 vs. 20.9 ± 0.7 pM, P > 0.05, n = 6). Nifedipine also eliminated depolarization driven GLP-1 responses to vascular KCl (50 mM) (KCl: 8.60 ± 0.4 vs. 47.8 ± 13.0 pM, P < 0.05, KCl+NI: 7.83 ± 0.49 vs. 15.23 ±1.32 pM, P < 0.05, n = 6). The non-metabolizable SGLT1 substrate, α-MGP, stimulated release (15.7 ± 0.5 vs. 29.4 ± 0.7 pM, P < 0.0001, n = 6), while both α-MGP and glucose failed to stimulate GLP-1 secretion in presence of the SGTL1 inhibitor phloridzin (10 μM) (P > 0.05). However, glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (1 mM phloretin) (Glu. 13.94 ± 2.5 vs. 30.90 ± 10.9 pM, Glu.+PT: 12.44 ± 1.3 vs. 17.18 ± 3.4 pM, P > 0.0001, n = 6), and KATP-channel closure by two sulfonylurea drugs stimulated GLP-1 release (tolbutamide: 14.7 ± 0.2 vs. 28.6 ± 5.2 pM; gliclazide: 15.2 ± 0.3 vs. 24.6 ± 2.4 pM, P < 0.05, n = 8). Our data indicates that SGLT1 activity is the driving force for glucose induced GLP-1 secretion, though secretory responses.",
keywords = "The Faculty of Health and Medical Sciences, Glucagon-Like Peptide 1, Glucose, Mechanisms of secretion",
author = "Kuhre, {Rune Ehrenreich} and Frost, {Charlotte Rasmussen} and Berit Svendsen and Holst, {Jens Juul}",
year = "2014",
month = "6",
doi = "10.2337/db14-1741-2092",
language = "English",
volume = "63",
pages = "A491",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "suppl 1",

}

RIS

TY - ABST

T1 - Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation

AU - Kuhre, Rune Ehrenreich

AU - Frost, Charlotte Rasmussen

AU - Svendsen, Berit

AU - Holst, Jens Juul

PY - 2014/6

Y1 - 2014/6

N2 - We characterized the mechanisms of glucose-stimulated glucagon-like peptide-1 (GLP-1) secretion from isolated rat small intestine perfused at constant rate. Luminal glucose (5 and 20 % (w/v)) stimulated secretion dose dependently (ΔGLP-15% (w/v): 4.77 ± 0.8 vs. GLP-120% (w/v): 18.5 ± 2.8 pM, P<0.0001, n = 6) at rates correlating with glucose absorption (R2: 5% (w/v) = 0.68,R2: 20% (w/v) = 0.87, P < 0.001, n = 6), independent of the osmotic load. Vascular glucose stimulated secretion at 15 mM (21.7 ± 0.5 vs. 25.2 ± 0.6 pmol/l, P < 0.001, n = 6), but not at 5 and 10 mM (P > 0.05). Luminal glucose activated voltage-gated calcium channels in the L-cells, as inhibition with nifedipine (NI; 10 μM) or hyperpolarization with diazoxide completely abolished secretory responses (Glu. 9.19 ± 0.6 vs. 25.1 ± 0.56 pM, P < 0.01, Glu.+NI: 7.90 ± 0.56 vs. 10.57 ± 1.92 pM, P > 0.05, n = 6) (Glu.: 12.0 ± 0.6 vs. 31.8 ± 1.9 pM, P < 0.05, Glu. + DZ: 20.1 ± 1.0 vs. 20.9 ± 0.7 pM, P > 0.05, n = 6). Nifedipine also eliminated depolarization driven GLP-1 responses to vascular KCl (50 mM) (KCl: 8.60 ± 0.4 vs. 47.8 ± 13.0 pM, P < 0.05, KCl+NI: 7.83 ± 0.49 vs. 15.23 ±1.32 pM, P < 0.05, n = 6). The non-metabolizable SGLT1 substrate, α-MGP, stimulated release (15.7 ± 0.5 vs. 29.4 ± 0.7 pM, P < 0.0001, n = 6), while both α-MGP and glucose failed to stimulate GLP-1 secretion in presence of the SGTL1 inhibitor phloridzin (10 μM) (P > 0.05). However, glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (1 mM phloretin) (Glu. 13.94 ± 2.5 vs. 30.90 ± 10.9 pM, Glu.+PT: 12.44 ± 1.3 vs. 17.18 ± 3.4 pM, P > 0.0001, n = 6), and KATP-channel closure by two sulfonylurea drugs stimulated GLP-1 release (tolbutamide: 14.7 ± 0.2 vs. 28.6 ± 5.2 pM; gliclazide: 15.2 ± 0.3 vs. 24.6 ± 2.4 pM, P < 0.05, n = 8). Our data indicates that SGLT1 activity is the driving force for glucose induced GLP-1 secretion, though secretory responses.

AB - We characterized the mechanisms of glucose-stimulated glucagon-like peptide-1 (GLP-1) secretion from isolated rat small intestine perfused at constant rate. Luminal glucose (5 and 20 % (w/v)) stimulated secretion dose dependently (ΔGLP-15% (w/v): 4.77 ± 0.8 vs. GLP-120% (w/v): 18.5 ± 2.8 pM, P<0.0001, n = 6) at rates correlating with glucose absorption (R2: 5% (w/v) = 0.68,R2: 20% (w/v) = 0.87, P < 0.001, n = 6), independent of the osmotic load. Vascular glucose stimulated secretion at 15 mM (21.7 ± 0.5 vs. 25.2 ± 0.6 pmol/l, P < 0.001, n = 6), but not at 5 and 10 mM (P > 0.05). Luminal glucose activated voltage-gated calcium channels in the L-cells, as inhibition with nifedipine (NI; 10 μM) or hyperpolarization with diazoxide completely abolished secretory responses (Glu. 9.19 ± 0.6 vs. 25.1 ± 0.56 pM, P < 0.01, Glu.+NI: 7.90 ± 0.56 vs. 10.57 ± 1.92 pM, P > 0.05, n = 6) (Glu.: 12.0 ± 0.6 vs. 31.8 ± 1.9 pM, P < 0.05, Glu. + DZ: 20.1 ± 1.0 vs. 20.9 ± 0.7 pM, P > 0.05, n = 6). Nifedipine also eliminated depolarization driven GLP-1 responses to vascular KCl (50 mM) (KCl: 8.60 ± 0.4 vs. 47.8 ± 13.0 pM, P < 0.05, KCl+NI: 7.83 ± 0.49 vs. 15.23 ±1.32 pM, P < 0.05, n = 6). The non-metabolizable SGLT1 substrate, α-MGP, stimulated release (15.7 ± 0.5 vs. 29.4 ± 0.7 pM, P < 0.0001, n = 6), while both α-MGP and glucose failed to stimulate GLP-1 secretion in presence of the SGTL1 inhibitor phloridzin (10 μM) (P > 0.05). However, glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (1 mM phloretin) (Glu. 13.94 ± 2.5 vs. 30.90 ± 10.9 pM, Glu.+PT: 12.44 ± 1.3 vs. 17.18 ± 3.4 pM, P > 0.0001, n = 6), and KATP-channel closure by two sulfonylurea drugs stimulated GLP-1 release (tolbutamide: 14.7 ± 0.2 vs. 28.6 ± 5.2 pM; gliclazide: 15.2 ± 0.3 vs. 24.6 ± 2.4 pM, P < 0.05, n = 8). Our data indicates that SGLT1 activity is the driving force for glucose induced GLP-1 secretion, though secretory responses.

KW - The Faculty of Health and Medical Sciences

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Mechanisms of secretion

U2 - 10.2337/db14-1741-2092

DO - 10.2337/db14-1741-2092

M3 - Conference abstract in journal

VL - 63

SP - A491

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - suppl 1

M1 - Abstract no 1915-P

ER -

ID: 227782470