title: Gastrin treatment stimulates β-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats.
abstract: β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm(2) vs. Px+V: 0.27 ± 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.
authors.affiliation: Laboratory of Diabetes and Experimental Endocrinology, Department of Clinical Sciences, University of Barcelona, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona. Spain. ntellez@ub.edu
authors.forename: Noèlia
authors.initials: N
authors.lastname: Téllez
authors.forename: Géraldine
authors.initials: G
authors.lastname: Joanny
authors.forename: Jéssica
authors.initials: J
authors.lastname: Escoriza
authors.forename: Marina
authors.initials: M
authors.lastname: Vilaseca
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy; D005755:Gastrins / Q000494:pharmacology / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000188:drug therapy*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010180:Pancreatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D005755:Gastrins; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D043886:Receptor, Cholecystokinin A; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C037856:gastrin heptadecapeptide, Leu(15)-