A disrupted cholecystokinin a receptor gene induces diabetes in
obese rats synergistically with odb1 gene.
Takiguchi, Soichi, Yutaka Takata, Nobuhiko Takahashi, Kazuhiro
Kataoka, Tsukasa Hirashima, Kazuya Kawano, Kyoko Miyasaka, Akihiro
Funakoshi, and Akira Kono.
Divisions of Chemotherapy and Gastroenterology, National Kyushu
Cancer Center, Fukuoka 815; Department of Clinical Physiology, Tokyo
Metropolitan Institute of Gerontology, Tokyo 173, Third Department of
Iiternal Medicine, Asahikawa Medical Callege, Asahikawa Hokkaido 078,
4Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd.
Tokushima 771-01, Japan
APStracts 4:0230E, 1997.
Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop hyperglycemia,
hyperinsulinemia and mild obesity, which is characteristic of human
non-insulin-dependent diabetes mellitus (NIDDM). We have shown that
two recessive genes,ODB1 mapped on the X chromosome and ODB2 mapped
on chromosome 14, are involved in the induction of the diabetes in
OLETF rats. Recently we found that OLETF rats are the naturally
occurring cholecystokinin type-A receptor (CCKAR) gene knockout rats.
In this paper, we focused on the genotype of CCKAR gene and the ODB1
gene in regulation of glucose hemeostasis in the F2 cross of the
OLETF rats. Relatively high plasma glucose levels were observed in F2
offspring with the homozygously disrupted CCKAR gene. A synergistic
effect for increasing plasma glucose levels in F2 rats between
disrupted CCKAR gene and the ODB1 gene was shown. The CCKAR gene was
found to map very close to ODB2 by a linkage analysis using
microsatellite markers. These results suggest that CCKAR gene
maintains normoglycemia in rats.
Received 14 July 1997; accepted in final form 9 October 1997.
APS Manuscript Number E328-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997