title: Ultrastructural localization of insulin-like growth factor-2 (IGF-2) to the secretory granules of insulin cells: a study in normal and diabetic (GK) rats.
abstract: By using biochemical and light-microscopical techniques, insulin-like growth factor-2 (IGF-2) has recently been found in adult pancreas, co-localized immunohistochemically with insulin in the islet B-cells. The purpose of this study was to trace IGF-2 immunoreactivity (IR) at the ultrastructural level in normal and diabetic Goto-Kakizaki (GK) rats. Using a pre-embedding technique and immuno-gold-silver staining, IGF-2 antibody binding was localized exclusively to the halo of a subset of secretory beta-granules in normal rats. Insulin IR occurred more frequently in the granules. GK rats had, in addition to normal-looking islets, some islets with irregular shape and an increased amount of fibrous tissue, so-called "starfish-shaped" islets. In these, beta-granules were usually found, but most of the B-cells were also occupied by large, usually electron-translucent vesicles, some resembling crinophagic bodies, i.e., the sign of intracellular degradation of secretory granules. In starfish-shaped islets, IGF-2 IR was localized to the halo of beta-granules, as in GK islets with normal appearance. Occasionally, IGF-2 IR was also found in the cytoplasm and even in adjacent fibroblasts. Insulin IR was restricted to beta-granules. Because the lysosomes have IGF-2 receptors, the presence of IGF-2 peptide in secretory granules could explain why some granules are guided to lysosomes for degradation.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden. anho@fafner.mb.ks.se
authors.forename: A
authors.initials: A
authors.lastname: Höög
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.forename: S M
authors.initials: SM
authors.lastname: Abdel-Halim
authors.forename: S
authors.initials: S
authors.lastname: Falkmer
authors.forename: L
authors.initials: L
authors.lastname: Qing
authors.forename: L
authors.initials: L
authors.lastname: Grimelius
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000737:chemistry* / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D007515:Islets of Langerhans / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
chemical_list: D007335:Insulin-Like Growth Factor II