BACKGROUND: After pancreatectomy, regeneration of acinar and islet elements occurs. Recent data from a model of islet hyperplasia in the hamster suggested that induction of a local pancreatic factor stimulates islet formation. We postulate that the reg gene may be this factor. METHODS: We studied reg expression during induction of islet growth by using a similar model in the rat. Rats underwent surgical wrapping of the splenic lobe of the pancreas or sham operation. RESULTS: At 2 days ductular proliferation and immunohistochemical evidence of insulin within ductular epithelia were evident in the wrapped lobe. By 14 and 56 days islet number per square millimeter increased 63% and 43%, respectively. Reg mRNA levels, measured by Northern blot analysis with a rat reg cDNA probe (n = 5), increased 300% at 2 days in the wrapped lobe and decreased to that of unwrapped controls by 14 days. In situ hybridization showed localization of reg to the acinar cells. In unwrapped gastric lobes of animals who underwent surgical wrapping of the splenic lobe, no change in islet number per square millimeter or reg gene expression was noted. CONCLUSIONS: Surgical wrapping of the pancreatic splenic lobe induces local reg gene expression that is temporally associated with duct cell hyperplasia. This is followed by islet formation within the wrapped lobe. Reg may play a role in the induction of new islets from ductular precursors and in maintenance of normal islet function.
BACKGROUND: After pancreatectomy, regeneration of acinar and islet elements occurs. Recent data from a model of islet hyperplasia in the hamster suggested that induction of a local pancreatic factor stimulates islet formation. We postulate that the reg gene may be this factor. METHODS: We studied reg expression during induction of islet growth by using a similar model in the rat. Rats underwent surgical wrapping of the splenic lobe of the pancreas or sham operation. RESULTS: At 2 days ductular proliferation and immunohistochemical evidence of insulin within ductular epithelia were evident in the wrapped lobe. By 14 and 56 days islet number per square millimeter increased 63% and 43%, respectively. Reg mRNA levels, measured by Northern blot analysis with a ratreg cDNA probe (n = 5), increased 300% at 2 days in the wrapped lobe and decreased to that of unwrapped controls by 14 days. In situ hybridization showed localization of reg to the acinar cells. In unwrapped gastric lobes of animals who underwent surgical wrapping of the splenic lobe, no change in islet number per square millimeter or reg gene expression was noted. CONCLUSIONS: Surgical wrapping of the pancreatic splenic lobe induces local reg gene expression that is temporally associated with duct cell hyperplasia. This is followed by islet formation within the wrapped lobe. Reg may play a role in the induction of new islets from ductular precursors and in maintenance of normal islet function.
Authors: Tomasz P Radon; Nathalie J Massat; Richard Jones; Wasfi Alrawashdeh; Laurent Dumartin; Darren Ennis; Stephen W Duffy; Hemant M Kocher; Stephen P Pereira; Luisa Guarner posthumous; Cristiane Murta-Nascimento; Francisco X Real; Núria Malats; John Neoptolemos; Eithne Costello; William Greenhalf; Nick R Lemoine; Tatjana Crnogorac-Jurcevic Journal: Clin Cancer Res Date: 2015-08-01 Impact factor: 12.531