title: Expression of cholecystokinin2-receptor in rat and human L cells and the stimulation of glucagon-like peptide-1 secretion by gastrin treatment.
abstract: Gastrin is a gastrointestinal hormone secreted by G cells. Hypergastrinemia can improve blood glucose and glycosylated hemoglobin levels. These positive effects are primarily due to the trophic effects of gastrin on β-cells. In recent years, many receptors that regulate secretion of glucagon-like peptide 1 (GLP-1) have been identified in enteroendocrine L cell lines. This led us to hypothesize that, in addition to the trophic effects of gastrin on β-cells, L cells also express cholecystokinin2-receptor (CCK2R), which may regulate GLP-1 secretion and have synergistic effects on glucose homeostasis. Our research provides a preliminary analysis of CCK2R expression and the stimulating effect of gastrin treatment on GLP-1 secretion in a human endocrine L cell line, using RT-PCR, Western blot, immunocytochemistry, and ELISA analyses. The expression of proglucagon and prohormone convertase 3, which regulate GLP-1 biosynthesis, were also analyzed by real-time PCR. Double immunofluorescence labeling was utilized to assess the intracellular localization of CCK2R and GLP-1 in L cells harvested from rat colon tissue. Our results showed that CCK2R was expressed in both the human L cell line and the rat L cells. We also showed that treatment with gastrin, a CCK2R agonist, stimulated the secretion of GLP-1, and that this effect was likely due to increased expression of proglucagon and PCSK1 (also known as prohormone convertase 3 (PC3 gene)). These results not only provide a basis for the role gastrin may play in intestinal L cells, and may also provide the basis for the development of a method of gastrin-mediated glycemic regulation.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China. Electronic address: liuxiaomin1957@126.com.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019858:Enteroendocrine Cells / Q000166:cytology / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D043887:Receptor, Cholecystokinin B / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005755:Gastrins; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D052216:Glucagon-Like Peptide 1
keywords: Cholecystokinin(2) receptor (CCK2R); Gastrin; Glucagon-like peptide-1 (GLP-1); NCI-H716 cell line; Rat colon