Early administration of keratinocyte growth factor improves {beta}-cell regeneration in rat with streptozotocin-induced diabetes.
The aim of our study was to investigate the ability of keratinocyte growth factor (KGF; palifermin) in regulating beta-cell growth in normal newborn rats and in rats with neonatal diabetes. Wistar rats were injected with streptozotocin (STZ) to induce diabetes on the dayof birth. From days 2 to 6 after birth, animals received a daily s.c. injection of KGF (STZ/KGF group) and at the dose of 3 mg/kg body weight or saline solution (STZ groups). A group of non-diabetic Wistar rats was treated either with saline (Wistar group) or with KGF from days 2 to 6 after birth at the dose of 3 mg/kg body weight (Wistar/KGF group). beta-cell mass was measured at day 7 after birth in all groups. beta- and ductal cells replication were measured in all groups and apoptosis was assessed in the pancreas of 2-, 4-, and 7-day-old STZ and STZ/KGF rats. The total beta-cell mass of the 7-day-old KGF/STZ neonates was significantly increased compared with that of age-matched STZ rats. beta-cell replication rate was decreased at day 2 in the STZ/KGF group and was similar in the 4- and 7-day-old rats from STZ and STZ/KGF groups. Duct cell replication was significantly increased in the pancreas of 2- and 4-day-old KGF/STZ neonates when compared with that of age-matched rats from STZ control group. The rate of apoptosis in the neonatal pancreases of STZ and KGF/STZ groups was not significantly different. In non-diabetic Wistar rats, KGF treatment led to a slight but significant increase in duct cell proliferation at day 2 without significant changes in the total beta-cell mass in the 7-day-old rats. We provide evidence for a growth-promoting effect of KGF during beta-cell regeneration in neonatal diabetic rats. KGF exerts strong mitogenic effect on the pancreatic duct cells, thus expanding the population of precursor cells that subsequently differentiate into insulin-producing beta-cells.
Movassat
Jamileh
J
Laboratoire de Physiopathologie de la Nutrition-CNRS/UMR 7059, Université Paris 7, 2, place Jussieu, 75005 Paris, France. movassat@paris7.jussieu.fr
Portha
Bernard
B
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D010179:Pancreas / Q000473:pathology; D010183:Pancreatic Ducts / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*
D051523:Fibroblast Growth Factor 7