title: Mitogenic effects of Brazilian arthropod venom on isolated islet beta cells: in vitro morphologic ultrastructural and functional studies.
abstract: BACKGROUND
  One of the major pitfalls associated with use of isolated adult islets of Langerhans' cells is their minimal mitotic capacity. Consequently, maintenance of a steady viable islet cell mass is very difficult. To explore how to enhance beta-cell mitogenesis, we have examined the effects of venom fractions extracted from a Brazilian scorpion on morphologic and functional beta-cell patterns. The venom was previously known to induce nesidioblastosis-like effects with chronic hypoglycemia and pancreatitis in animal models.
  
  
  METHODS
  Venom fractions purified from Tityus bahiensis were incubated with batches of isolated rat islets, while a morphologic examination, glucose-stimulated insulin release, insulin content, and insulin messenger ribonucleic acid (mRNA) were carried out early during incubation. On fixation and double fluorescence immunolabeling (rhodamine for anti-insulin monoclonal antibodies; fluorescein for anti-5-bromodeoxyuridine), the preparations were imaged by confocal laser microscopy (CLM) for morphometric quantification of the mitoses. Insulin recovery and mRNA were also assessed at 21 days of culture.
  
  
  RESULTS
  Under CLM examination, the beta-cell mitotic rate significantly rose from 1 to 12.8% for the venom-exposed islets. At day 7, insulin release and content were significantly lower for the venom-exposed than the control islets. However, at day 21 of culture, insulin release in response to static incubation with glucose and insulin mRNA from the venom-exposed islets was higher than controls (p < .05).
  
  
  CONCLUSIONS
  Incubation with the scorpion venom induced a rapid and significant increase in the beta-cell proliferation not associated with a short-term increase in insulin secretion. The latter fully resumed and overcame controls later in culture, possibly after completion of the beta-cell expansion process.
authors.affiliation: Department of Internal Medicine, University of Perugia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luca
authors.forename: Mario
authors.initials: M
authors.lastname: Calvitti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basta
authors.forename: Tiziano
authors.initials: T
authors.lastname: Baroni
authors.forename: Luca M
authors.initials: LM
authors.lastname: Neri
authors.forename: Ennio
authors.initials: E
authors.lastname: Becchetti
authors.forename: Silvano
authors.initials: S
authors.lastname: Capitani
authors.forename: Geovana
authors.initials: G
authors.lastname: Novaes
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Correa-Giannella
authors.forename: Evanguedes
authors.initials: E
authors.lastname: Kalapothakis
authors.forename: Sylva Stuchi Maria
authors.initials: SS
authors.lastname: Engler
authors.forename: Freddy Goldberg
authors.initials: FG
authors.lastname: Eliaschewitz
authors.forename: Mari Cleide
authors.initials: MC
authors.lastname: Sogayar
authors.forename: Carmine
authors.initials: C
authors.lastname: Fanelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Brunetti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calafiore
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008934:Mitogens / Q000737:chemistry / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000737:chemistry / Q000633:toxicity*; D012605:Scorpions / Q000502:physiology*
chemical_list: D007328:Insulin; D008934:Mitogens; D012333:RNA, Messenger; D012604:Scorpion Venoms; D001973:Bromodeoxyuridine