Administration of Conophylline and Betacellulin-δ4 Increases the β-cell Mass in Neonatal Streptozotocin-treated Rats

The present study was conducted to examine the effect of administration of conophylline (CnP) and betacellulinδ4 (BTCδ4) on the β-cell mass in neonatal streptozotocin-treated rats (neonatal sTz rats). sTz (100 μg/g) was injected into neonatal rats, and then CnP (2 μg/g) and/or BTCδ4 (200 pmol/g) were administered to neonatal sTz rats for 1 week. The plasma glucose concentration was monitored, and an intraperitoneal glucose tolerance test (ipGTT) was performed on day 8 and at 8 weeks after the sTz injection. In neonatal sTz rats treated with control solution (s group), the plasma glucose concentration increased for several days after the sTz injection, returned to nearly normal levels, and then increased gradually after six weeks of age. eight weeks after the sTz-injection, the plasma glucose concentration was increased significantly compared to that of normal rats. The glucose response to ipGTT was significantly reduced in neonatal sTz rats treated with CnP (CnP group), BTCδ4 (δ4 group) and CnP+BTCδ4 (CnP+δ4 group). The β-cell mass and the insulin content of the pancreas were significantly increased in the CnP group and δ4 group. The effect of CnP+δ4 was greater than that of CnP alone or BTCδ4 alone. CnP+BTCδ4 significantly increased the number of PDX-1-positive ductal cells and the number of insulin/BrdU double-positive ductal cells. These results indicate the efficacy of CnP and BTCδ4 in increasing the β-cells mass of neonatal sTz-treated rats.