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J Investig Med ; 51(2): 79-85, 2003 Mar.
Article de Anglais | MEDLINE | ID: mdl-12643512

RÉSUMÉ

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.


Sujet(s)
Ilots pancréatiques/effets des médicaments et des substances chimiques , Mitogènes/toxicité , Venins de scorpion/toxicité , Scorpions/physiologie , Animaux , Broxuridine/métabolisme , Numération cellulaire , Division cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Relation dose-effet des médicaments , Insuline/analyse , Insuline/génétique , Insuline/métabolisme , Sécrétion d'insuline , Ilots pancréatiques/métabolisme , Ilots pancréatiques/anatomopathologie , Mâle , Microscopie confocale , Mitogènes/composition chimique , ARN messager/métabolisme , Rats , Rat Sprague-Dawley , Venins de scorpion/composition chimique
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