[Age-dependent alteration of insulin and ghrelin expression in pancreatic islets of intrauterine growth-retarded rats].
To evaluate the age-dependent alteration of insulin and ghrelin expression in the pancreatic islets of intrauterine growth-retarded (IUGR) rats during development and to identify the role of ghrelin in insulin resistance induced by IUGR.



Neonatal SD rats were divided into normal birth weight group (N group) and intrauterine growth-retarded group (I group). Plasma glucose, ghrelin and serum insulin were analyzed at day 1, 3, 7 and 10 and at week 2, 3, 4,8 and 12 after birth.Entire pancreas samples were collected for determination of ghrelin and insulin mRNA. Immunohistochemical double-staining and confocal microscopy was performed on rat pancreas.



Plasma insulin levels of I group were lower than those of N group at day 1, 3 and 7 (P <0.05). The homeostasis model assessment-insulin resistance index (HOMA-IR) of I group was higher than that of N group at day 1, 3 and 7 (P<0.05). Plasma glucose levels, insulin, HOMA-IR and ghrelin concentrations decreased in an age-dependent manner (F = 4.12 to approximately 125.97, P <0.001) in both groups. Plasma ghrelin level was correlated with HOMA-IR in I group(r=0.553, P=0.000). Pancreatic ghrelin contents, pancreatic ghrelin mRNA expression, the percentage of insulin (+) cells and ghrelin (+) cells in both groups decreased in an age-dependent manner (F = -49.29 to approximately 427.28, P<0.001). There were differences in the above indexes between N and I group (F = -69.98 to approximately 169.22, P<0.05). Insulin secretion was negatively correlated with ghrelin contents in both groups (r=-0.895, P=0.000; r=-0.458, P=0.002). Percentage of insulin(+) cells was negatively correlated with the percentage of ghrelin (+) cells in pancreatic islets in both groups (r=-0.810,P=0.000; r=-0.714, P=0.000). The distributions of ghrelin (+) cells in pancreatic islets of I group were different from those of N group.



The effects of IUGR on weight, plasma ghrelin levels and insulin secretion of pups rats persist after birth and ghrelin may be involved in the process of insulin resistance in IUGR rats.
Department of Endocrinology, The Affiliated Children's Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Xiu-Min
XM
Wang
Li
L
Liang
Li-Zhong
LZ
Du
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D054439:Ghrelin / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D054439:Ghrelin; D007328:Insulin; D012333:RNA, Messenger