title: Potent inhibitory effects of transplantable rat glucagonomas and insulinomas on the respective endogenous islet cells are associated with pancreatic apoptosis.
abstract: Effects of transplantable rat insulinomas (IN) and glucagonomas (GLU) on the endogenous pancreas were analyzed using morphometry, immunocytochemistry, in situ hybridization, and staining for apoptotic cells. Hyperinsulinemia (IN-rats) and hyper-GLP-1/glucagonemia (GLU-rats) were both associated with marked islet atrophy (67 and 76% of control average planimetrical islet area, respectively). Selective islet B cell inhibition of proinsulin (I and II) genes as well as of expression of the insulin gene transcription factor, IPF1/STF1, was found in IN-rats. Moreover, these islets were characterized by significant B cells apoptosis in the absence of infiltrating lymphocytes. In GLU-rats selective islet A cell inhibition was observed at the level of glucagon mRNA. These islets contained small, highly condensed but clearly active B cells with prominent IPF1/STF1-positive nuclei, surrounded by densely packed glucagon-negative cells with reduced cytoplasm. Furthermore, an active apoptotic process was found exclusively in the exocrine pancreas of GLU-rats. Thus, in IN-rats, islet B cell mass reduction is distinguished by non-immune-mediated programmed cell death, while GLU-rats exhibit A cell mass reduction by cytoplasmic retraction and selective exocrine apoptosis.
authors.affiliation: Hagedorn Research Institute, Gentofte, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Blume
authors.forename: J
authors.initials: J
authors.lastname: Skouv
authors.forename: L I
authors.initials: LI
authors.lastname: Larsson
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: O D
authors.initials: OD
authors.lastname: Madsen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017690:Cell Transplantation; D005786:Gene Expression Regulation; D005935:Glucagonoma / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D007340:Insulinoma / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000473:pathology*; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D011384:Proinsulin / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
chemical_list: D007328:Insulin; D011384:Proinsulin