Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats.

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Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats. / Simonsen, Lotte; Pilgaard, Sofie; Orskov, Cathrine; Rosenkilde, Mette M; Hartmann, Bolette; Holst, Jens J; Deacon, Carolyn F.

In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 293, No. 1, 2007, p. G288-95.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Simonsen, L, Pilgaard, S, Orskov, C, Rosenkilde, MM, Hartmann, B, Holst, JJ & Deacon, CF 2007, 'Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats.', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 293, no. 1, pp. G288-95. https://doi.org/10.1152/ajpgi.00453.2006

APA

Simonsen, L., Pilgaard, S., Orskov, C., Rosenkilde, M. M., Hartmann, B., Holst, J. J., & Deacon, C. F. (2007). Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats. American Journal of Physiology: Gastrointestinal and Liver Physiology, 293(1), G288-95. https://doi.org/10.1152/ajpgi.00453.2006

Vancouver

Simonsen L, Pilgaard S, Orskov C, Rosenkilde MM, Hartmann B, Holst JJ et al. Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats. American Journal of Physiology: Gastrointestinal and Liver Physiology. 2007;293(1):G288-95. https://doi.org/10.1152/ajpgi.00453.2006

Author

Simonsen, Lotte ; Pilgaard, Sofie ; Orskov, Cathrine ; Rosenkilde, Mette M ; Hartmann, Bolette ; Holst, Jens J ; Deacon, Carolyn F. / Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats. In: American Journal of Physiology: Gastrointestinal and Liver Physiology. 2007 ; Vol. 293, No. 1. pp. G288-95.

Bibtex

@article{8b08b970ab4911ddb5e9000ea68e967b,
title = "Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats.",
abstract = "Long-term treatment with dipeptidyl peptidase IV inhibitors (DPPIV-I) or glucagon-like peptide (GLP)-1 analogs may potentially affect intestinal growth by down- or upregulating the intestinotrophic hormone GLP-2. This study compared the intestinotrophic effects of 12-wk administration of vehicle, exendin-4 (Ex-4; 5 nmol/kg bid sc), or DPPIV-I (NN-7201, 10 mg/kg qd orally) in GK rats. Some animals were observed additionally for 9 wk after the end of treatment. Both treatments lowered glycated hemoglobin A1c at wk 12 vs. control (Ex-4, -0.8{\%}; DPPIV-I, -0.4{\%}). Body weight was reduced by Ex-4 compared with control (361 +/- 4 vs. 399 +/- 5 g; P < 0.001) because of reduced food intake, whereas neither parameter was affected by DPPIV-I. Linear bone growth was unaffected by either treatment. After treatment end, food intake in Ex-4 animals increased, and, by wk 21, body weight was identical in all groups. The small intestine of Ex-4-treated animals was larger at wk 12 compared with control (length, 135.6 +/- 1.6 vs. 124.5 +/- 2.3 cm, P < 0.001; absolute weight, 8.4 +/- 0.2 vs. 6.4 +/- 0.4 g, P < 0.001), being most pronounced proximally, where the absolute cross-sectional area related to body weight increased by 24{\%} because of increased mucosal thickness. These effects were reversible, and 9 wk after the end of treatment, no differences between Ex-4 and control were apparent. Plasma GLP-2 concentrations were unaltered by either treatment, and Ex-4 had no agonistic or antagonistic effects on the transfected GLP-2 receptor. DPPIV-I had no intestinal effects. In conclusion, the continued presence of Ex-4 is necessary to maintain weight loss in GK rats. Effective antihyperglycemic treatment with Ex-4 increases intestinal mass reversibly, whereas DPPIV-I lacks intestinal effects.",
author = "Lotte Simonsen and Sofie Pilgaard and Cathrine Orskov and Rosenkilde, {Mette M} and Bolette Hartmann and Holst, {Jens J} and Deacon, {Carolyn F}",
note = "Keywords: Animals; Antigens, CD26; Body Weight; COS Cells; Cell Proliferation; Cercopithecus aethiops; Cyclic AMP; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Eating; Hemoglobin A, Glycosylated; Humans; Intestine, Small; Male; Peptides; Protease Inhibitors; Rats; Receptors, Glucagon; Transfection; Venoms; Xanthines",
year = "2007",
doi = "10.1152/ajpgi.00453.2006",
language = "English",
volume = "293",
pages = "G288--95",
journal = "American Journal of Physiology: Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "1",

}

RIS

TY - JOUR

T1 - Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats.

AU - Simonsen, Lotte

AU - Pilgaard, Sofie

AU - Orskov, Cathrine

AU - Rosenkilde, Mette M

AU - Hartmann, Bolette

AU - Holst, Jens J

AU - Deacon, Carolyn F

N1 - Keywords: Animals; Antigens, CD26; Body Weight; COS Cells; Cell Proliferation; Cercopithecus aethiops; Cyclic AMP; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Eating; Hemoglobin A, Glycosylated; Humans; Intestine, Small; Male; Peptides; Protease Inhibitors; Rats; Receptors, Glucagon; Transfection; Venoms; Xanthines

PY - 2007

Y1 - 2007

N2 - Long-term treatment with dipeptidyl peptidase IV inhibitors (DPPIV-I) or glucagon-like peptide (GLP)-1 analogs may potentially affect intestinal growth by down- or upregulating the intestinotrophic hormone GLP-2. This study compared the intestinotrophic effects of 12-wk administration of vehicle, exendin-4 (Ex-4; 5 nmol/kg bid sc), or DPPIV-I (NN-7201, 10 mg/kg qd orally) in GK rats. Some animals were observed additionally for 9 wk after the end of treatment. Both treatments lowered glycated hemoglobin A1c at wk 12 vs. control (Ex-4, -0.8%; DPPIV-I, -0.4%). Body weight was reduced by Ex-4 compared with control (361 +/- 4 vs. 399 +/- 5 g; P < 0.001) because of reduced food intake, whereas neither parameter was affected by DPPIV-I. Linear bone growth was unaffected by either treatment. After treatment end, food intake in Ex-4 animals increased, and, by wk 21, body weight was identical in all groups. The small intestine of Ex-4-treated animals was larger at wk 12 compared with control (length, 135.6 +/- 1.6 vs. 124.5 +/- 2.3 cm, P < 0.001; absolute weight, 8.4 +/- 0.2 vs. 6.4 +/- 0.4 g, P < 0.001), being most pronounced proximally, where the absolute cross-sectional area related to body weight increased by 24% because of increased mucosal thickness. These effects were reversible, and 9 wk after the end of treatment, no differences between Ex-4 and control were apparent. Plasma GLP-2 concentrations were unaltered by either treatment, and Ex-4 had no agonistic or antagonistic effects on the transfected GLP-2 receptor. DPPIV-I had no intestinal effects. In conclusion, the continued presence of Ex-4 is necessary to maintain weight loss in GK rats. Effective antihyperglycemic treatment with Ex-4 increases intestinal mass reversibly, whereas DPPIV-I lacks intestinal effects.

AB - Long-term treatment with dipeptidyl peptidase IV inhibitors (DPPIV-I) or glucagon-like peptide (GLP)-1 analogs may potentially affect intestinal growth by down- or upregulating the intestinotrophic hormone GLP-2. This study compared the intestinotrophic effects of 12-wk administration of vehicle, exendin-4 (Ex-4; 5 nmol/kg bid sc), or DPPIV-I (NN-7201, 10 mg/kg qd orally) in GK rats. Some animals were observed additionally for 9 wk after the end of treatment. Both treatments lowered glycated hemoglobin A1c at wk 12 vs. control (Ex-4, -0.8%; DPPIV-I, -0.4%). Body weight was reduced by Ex-4 compared with control (361 +/- 4 vs. 399 +/- 5 g; P < 0.001) because of reduced food intake, whereas neither parameter was affected by DPPIV-I. Linear bone growth was unaffected by either treatment. After treatment end, food intake in Ex-4 animals increased, and, by wk 21, body weight was identical in all groups. The small intestine of Ex-4-treated animals was larger at wk 12 compared with control (length, 135.6 +/- 1.6 vs. 124.5 +/- 2.3 cm, P < 0.001; absolute weight, 8.4 +/- 0.2 vs. 6.4 +/- 0.4 g, P < 0.001), being most pronounced proximally, where the absolute cross-sectional area related to body weight increased by 24% because of increased mucosal thickness. These effects were reversible, and 9 wk after the end of treatment, no differences between Ex-4 and control were apparent. Plasma GLP-2 concentrations were unaltered by either treatment, and Ex-4 had no agonistic or antagonistic effects on the transfected GLP-2 receptor. DPPIV-I had no intestinal effects. In conclusion, the continued presence of Ex-4 is necessary to maintain weight loss in GK rats. Effective antihyperglycemic treatment with Ex-4 increases intestinal mass reversibly, whereas DPPIV-I lacks intestinal effects.

U2 - 10.1152/ajpgi.00453.2006

DO - 10.1152/ajpgi.00453.2006

M3 - Journal article

VL - 293

SP - G288-95

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 1

ER -

ID: 8416942