Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor.
Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.
Funakoshi
A
A
Department of Gastroenterology, National Kyushu Cancer Center, Fukuoka, Japan.
Miyasaka
K
K
Kanai
S
S
Masuda
M
M
Yasunami
Y
Y
Nagai
T
T
Ikeda
S
S
Jimi
A
A
Kawanami
T
T
Kono
A
A
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D002766:Cholecystokinin / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D005502:Food; D015870:Gene Expression; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008969:Molecular Sequence Data; D010182:Pancreatic Diseases / Q000378:metabolism / Q000503:physiopathology*; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000032:analysis*
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D005934:Glucagon; D002766:Cholecystokinin