title: Genetic verification of the role of CCK-AR in pancreatic proliferation and blood glucose and insulin regulation using a congenic rat carrying CCK-AR null allele.
abstract: A number of studies have indicated that cholecystokinin type A receptor (CCK-AR) plays a crucial role in postnatal pancreatic proliferation and blood glucose regulation through stimulating insulin secretion. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been shown to possess poor pancreatic proliferation (PPP) capability after pancreatectomy (Px). Here we have constructed a congenic strain which introgressed an OLETF-derived 18.5 cM genomic fragment identified in our previous quantitative trait locus (QTL) analysis as a locus responsible for PPP into normoglycemic F344 genetic background The introgressed region includes CCK-AR null mutation. After Px, the congenic rat showed weak pancreatic proliferation equivalent to that of the OLETF rat. Furthermore, post-surgery non-fasting blood glucose levels for the congenic rats are significantly higher in comparison with the F344 rats. At 28 days after Px, the congenic rats also showed lower blood insulin levels than the F344 rats. These results further provide the genetic evidence that 1) CCK-AR is essential for pancreatic regeneration; 2) impaired pancreatic proliferation mediates the development of hyperglycemia.
authors.affiliation: Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto, Tokushima 770-8503, Japan.
authors.forename: D H
authors.initials: DH
authors.lastname: Moralejo
authors.forename: T
authors.initials: T
authors.lastname: Ogino
authors.forename: H
authors.initials: H
authors.lastname: Kose
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000483:Alleles; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D007328:Insulin / Q000097:blood*; D008297:Male; D010179:Pancreas / Q000502:physiology*; D010180:Pancreatectomy; D051381:Rats; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin