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Mitogenic Effects of Brazilian Arthropod Venom on Isolated Islet Beta Cells: In Vitro Morphologic Ultrastructural and Functional Studies
  1. Giovanni Luca,
  2. Mario Calvitti,
  3. Giuseppe Basta,
  4. Tiziano Baroni,
  5. Luca M. Neri,
  6. Ennio Becchetti,
  7. Silvano Capitani,
  8. Geovana Novaes,
  9. Maria Lucia Correa-Giannella,
  10. Evanguedes Kalapothakis,
  11. Sylva Stuchi Maria Engler,
  12. Freddy Goldberg Eliaschewitz,
  13. Mari Cleide Sogayar,
  14. Carmine Fanelli,
  15. Paolo Brunetti,
  16. Riccardo Calafiore
  1. From the Departments of Internal Medicine (G.L., G.B., C.F., P.B., R.C.), Section of Internal Medicine and Endocrine and Metabolic Sciences (Di.M.I.), and Experimental Medicine and Biochemical Sciences (M. C., T.B., E.B.), University of Perugia, Perugia, Italy; Department of Morphology and Embryology (L.M.N., S.C.), Section of Human Anatomy, University of Ferrara, Ferrara, Italy, and Consorzio Interuniversitario per i Trapianti d'Organo, Rome, Italy; Federal University of Bahia (G.N.), Department of Pharmacology (E.K.), Bahia; Federal University of Minas Gerais, Minas Gerais; Institute of Chemistry (M.L.C.-G., S.S. M.E., M.C.S.), University of San Paulo, Sao Paulo, Brazil; Hospital Heliòpolis (F.G.E.), San Paulo, Brazil.
  1. This work was supported by grant EC.0562 from Telethon Italia (R.C.), Telethon Foundation, and a grant from the Italian Ministry for Instruction, University and Scientific and Technological Research, Rome, Italy.
  2. Address for correspondence: Dr. Riccardo Calafiore, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy. E-mail: islet{at}


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 mitoge-nesis, 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 nesidioblas-tosis-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 morphome- trie 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.

Key Words
  • insulin
  • diabetes mellitus
  • transplantation
  • cell growth and differentiation
  • blood glucose

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