Effects of atorvastatin on the regeneration of pancreatic {beta}-cells after streptozotocin treatment in the neonatal rodent.
To investigate the role of statins in beta-cell regeneration a model of streptozotocin (STZ)-induced beta-cell injury was used in the neonatal rat. We hypothesized that beta-cell growth and regeneration would increase following treatment with atorvastatin and that this would be associated with intraislet vasculogenesis. Pregnant Wistar rats were gavaged with 20 or 40 mg/kg atorvastatin for 21 days commencing on gestation day 15. Atorvastatin was detected in the circulation of the offspring. On postnatal day 4, the pups were given either a control or STZ (70 mg/kg ip) injection. beta-Cell mass had partially recovered by postnatal day 44 following STZ treatment, and atorvastatin (20 mg/kg) significantly increased beta-cell mass in both STZ-treated and control animals. An increase in the numbers of small islets at postnatal day 44 was seen in STZ-treated animals following atorvastatin, suggestive of neogenesis, and glucose tolerance was improved. Treatment with atorvastatin caused an increase in the numbers of intraislet endothelial cells at postnatal day 14 and the percentage of endothelial cells undergoing DNA synthesis, suggesting that angiogenesis had preceded the increase in beta-cell mass. The results indicate that functional beta-cell mass was expanded with atorvastatin in both control and STZ-treated neonatal rats and suggests a novel effect of a statin in promoting islet plasticity.
Marchand
K C
KC
Lawson Health Research Institute, St. Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada.
Arany
E J
EJ
Hill
D J
DJ
D000818:Animals; D000831:Animals, Newborn; D000069059:Atorvastatin; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D005260:Female; D005951:Glucose Tolerance Test; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D000069059:Atorvastatin