Linked Life Data

15780432

Source:http://linkedlifedata.com/resource/pubmed/id/15780432

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-3-22
pubmed:abstractText
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut-derived incretins secreted in response to nutrient ingestion. Both incretins potentiate glucose-dependent insulin secretion and enhance beta-cell mass through regulation of beta-cell proliferation, neogenesis and apoptosis. In contrast, GLP-1, but not GIP, inhibits gastric emptying, glucagon secretion, and food intake. Furthermore, human subjects with Type 2 diabetes exhibit relative resistance to the actions of GIP, but not GLP-1R agonists. The physiological importance of both incretins has been investigated through generation and analysis of incretin receptor knockout mice. Elimination of incretin receptor action in GIPR-/- or GLP-1R-/- mice produces only modest impairment in glucose homeostasis. Similarly, double incretin receptor knockout (DIRKO) mice exhibit normal body weight and normal levels of plasma glucagon and hypoglycemic responses to exogenous insulin. However, glucose-stimulated insulin secretion is significantly decreased following oral but not intraperitoneal glucose challenge in DIRKO mice and the glucose lowering actions of dipeptidyl peptidase-IV (DPP-IV) inhibitors are extinguished in DIRKO mice. Hence, incretin receptor signaling exerts physiologically relevant actions critical for glucose homeostasis, and represents a pharmacologically attractive target for development of agents for the treatment of Type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Gastric Inhibitory Polypeptide, http://linkedlifedata.com/resource/pubmed/chemical/Gastrointestinal Hormones, http://linkedlifedata.com/resource/pubmed/chemical/Glucagon, http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Gastrointestinal Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon, http://linkedlifedata.com/resource/pubmed/chemical/gastric inhibitory polypeptide..., http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide receptor
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0167-0115
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
125-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice.
pubmed:affiliation
Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, and the University of Toronto, 200 Elizabeth Street MBRW4R-402, Toronto, Ontario, Canada M5G 2C4.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't