Activin A and betacellulin: effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats.
Activin A and betacellulin (BTC) are thought to regulate differentiation of pancreatic beta-cells during development and regeneration of beta-cells in adults. In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells. One-day-old Sprague-Dawley rats were injected with STZ (85 micro g/g) and then administered for 7 days with activin A and/or BTC. Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading. The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months. Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and delta-cells. The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC. In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased. These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabolism in adults.
Li
Lei
L
Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Yi
Zhaohong
Z
Seno
Masaharu
M
Kojima
Itaru
I
D028341:Activins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002482:Cellulose / Q000378:metabolism* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D028322:Inhibin-beta Subunits / Q000378:metabolism* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*
C422405:activin A; D028341:Activins; D002482:Cellulose; D028322:Inhibin-beta Subunits