Oligodeoxynucleotide IMT504 induces a marked recovery of STZ-induced diabetes in rats: correlation with an early increase in the expression of nestin and Ngn3 progenitor cell markers.

BIANCHI MS; HERNANDO-INSÚA A; CHASSEING NA; RODRÍGUEZ JM; ELÍAS F; LAGO N; ZORZOPULOS J; LIBERTUN C; MONTANER AD; LUX-LANTOS VA

DIABETOLOGIA

Springer

Lugar: Berlin /Heidelberg; Año: 2010 vol. 53 p. 1184 - 1189

0012-186X

Aims/hypothesis: IMT504 is an oligonucleotide that promotes tissue repair in bone injury and neuropathic pain models by stimulating progenitor cells. Here we evaluated the effect of IMT504 on the recovery of streptozotocin (STZ)-induced diabetes. Methods: Male Sprague-Dawley rats were injected with STZ (60 mg/kg, i.p., day 1) or citrate buffer (Control). Animals with glycaemia between 11-20 mM on day 4 were injected with IMT504 (4 mg/animal in saline, s.c., STZ-IMT504) or with saline (STZ-Saline) for 10 days. Glycaemia, water and food intakes were recorded for 33 days. Glucose tolerance tests (IPGTT) were performed on day 30. On day 35, overnight-fasted animals were killed and blood samples and pancreases collected for hormonal and histological studies. A second group of STZ-IMT504 was killed, together with Control and STZ-Saline rats, after two consecutive days of blood glucose decreases after the beginning of IMT504 treatment. Pancreases were collected and proliferating cell nuclear antigen (PCNA), nestin and neurogenin3 (Ngn3) detected by immunohistochemistry. Results: IMT504 greatly improved blood glucose and food and water intakes in STZ-IMT504 by day 8, as well as IPGTTs on day 30. Significant increases in islet number and beta cell content were observed in STZ-IMT504 (day 33). Furthermore, after 2-5 IMT504 injections, blood glucose decreased and an increase in pancreatic nestin (mainly in endothelial cells), PCNA and Ngn3 expression (in islets) was observed in STZ-IMT504. Conclusions/interpretation: IMT504 induced a marked recovery of STZ-induced diabetes which correlated with early expression of progenitor cell markers, such as nestin and Ngn3.