Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice.
Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.
Miyawaki
K
K
Department of Metabolism, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Yamada
Y
Y
Yano
H
H
Niwa
H
H
Ban
N
N
Ihara
Y
Y
Kubota
A
A
Fujimoto
S
S
Kajikawa
M
M
Kuroe
A
A
Tsuda
K
K
Hashimoto
H
H
Yamashita
T
T
Jomori
T
T
Tashiro
F
F
Miyazaki
J
J
Seino
Y
Y
D000284:Administration, Oral; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004041:Dietary Fats; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007422:Intestines / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
D004041:Dietary Fats; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D011964:Receptors, Gastrointestinal Hormone; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C041086:gastric inhibitory polypeptide receptor; D005947:Glucose