Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors

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Standard

Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. / Hansotia, Tanya; Baggio, Laurie L; Delmeire, Dominique; Hinke, Simon A; Yamada, Yuichiro; Tsukiyama, Katsushi; Seino, Yutaka; Holst, Jens Juul; Schuit, Frans; Drucker, D J.

I: Diabetes, Bind 53, Nr. 5, 05.2004, s. 1326-35.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Hansotia, T, Baggio, LL, Delmeire, D, Hinke, SA, Yamada, Y, Tsukiyama, K, Seino, Y, Holst, JJ, Schuit, F & Drucker, DJ 2004, 'Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors', Diabetes, bind 53, nr. 5, s. 1326-35.

APA

Hansotia, T., Baggio, L. L., Delmeire, D., Hinke, S. A., Yamada, Y., Tsukiyama, K., Seino, Y., Holst, J. J., Schuit, F., & Drucker, D. J. (2004). Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes, 53(5), 1326-35.

Vancouver

Hansotia T, Baggio LL, Delmeire D, Hinke SA, Yamada Y, Tsukiyama K o.a. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes. 2004 maj;53(5):1326-35.

Author

Hansotia, Tanya ; Baggio, Laurie L ; Delmeire, Dominique ; Hinke, Simon A ; Yamada, Yuichiro ; Tsukiyama, Katsushi ; Seino, Yutaka ; Holst, Jens Juul ; Schuit, Frans ; Drucker, D J. / Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. I: Diabetes. 2004 ; Bind 53, Nr. 5. s. 1326-35.

Bibtex

@article{54fd5035f2854644a146dddec25de817,
title = "Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors",
abstract = "Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. We have now studied glucose homeostasis in double incretin receptor knockout (DIRKO) mice. DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. Plasma glucagon and the hypoglycemic response to exogenous insulin were normal in DIRKO mice. Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. Similarly, glucose-stimulated insulin secretion and the response to forskolin were well preserved in perifused DIRKO islets. Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors.",
keywords = "Animals, Dipeptidyl Peptidase 4, Enzyme Inhibitors, Glucose, Homeostasis, Insulin, Intestines, Islets of Langerhans, Mice, Mice, Inbred C57BL, Mice, Knockout, Organic Chemicals, Peptides, Pyrroles, Receptors, Gastrointestinal Hormone, Receptors, Glucagon, Valine, Venoms",
author = "Tanya Hansotia and Baggio, {Laurie L} and Dominique Delmeire and Hinke, {Simon A} and Yuichiro Yamada and Katsushi Tsukiyama and Yutaka Seino and Holst, {Jens Juul} and Frans Schuit and Drucker, {D J}",
year = "2004",
month = may,
language = "English",
volume = "53",
pages = "1326--35",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "5",

}

RIS

TY - JOUR

T1 - Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors

AU - Hansotia, Tanya

AU - Baggio, Laurie L

AU - Delmeire, Dominique

AU - Hinke, Simon A

AU - Yamada, Yuichiro

AU - Tsukiyama, Katsushi

AU - Seino, Yutaka

AU - Holst, Jens Juul

AU - Schuit, Frans

AU - Drucker, D J

PY - 2004/5

Y1 - 2004/5

N2 - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. We have now studied glucose homeostasis in double incretin receptor knockout (DIRKO) mice. DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. Plasma glucagon and the hypoglycemic response to exogenous insulin were normal in DIRKO mice. Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. Similarly, glucose-stimulated insulin secretion and the response to forskolin were well preserved in perifused DIRKO islets. Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors.

AB - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. We have now studied glucose homeostasis in double incretin receptor knockout (DIRKO) mice. DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. Plasma glucagon and the hypoglycemic response to exogenous insulin were normal in DIRKO mice. Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. Similarly, glucose-stimulated insulin secretion and the response to forskolin were well preserved in perifused DIRKO islets. Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors.

KW - Animals

KW - Dipeptidyl Peptidase 4

KW - Enzyme Inhibitors

KW - Glucose

KW - Homeostasis

KW - Insulin

KW - Intestines

KW - Islets of Langerhans

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Organic Chemicals

KW - Peptides

KW - Pyrroles

KW - Receptors, Gastrointestinal Hormone

KW - Receptors, Glucagon

KW - Valine

KW - Venoms

M3 - Journal article

C2 - 15111503

VL - 53

SP - 1326

EP - 1335

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -

ID: 132054503