The effects of intrauterine undernutrition on pancreas ghrelin and insulin expression in neonate rats

Abstract

Ghrelin has a correlation with insulin secretion, β-cell development, and diabetes in crucial development period. The aim of this study was to compare the changes in plasma ghrelin, insulin, and glucose concentrations, and variation of ghrelin expression in the pancreas in response to intrauterine malnutrition in newborn rats. Pregnant rats at day 2 were randomly divided into two groups: nourished (fed ad libitum; NR) and undernourished rats (UR). The offspring of NR were defined as normal-birth-weight group (NBW, n = 79) and those of UR were defined as low-birth-weight group (LBW, n = 74). Plasma glucose, ghrelin, and serum insulin of both dams and their pups were analyzed at the first day after birth. The entire pancreas was collected for determination of ghrelin and insulin mRNAs, and quantification of pancreas ghrelin and insulin. Immunohistochemical double staining and confocal microscopy were performed on rat pancreas. Birth weight was 5.81 ± 0.64 and 4.76 ± 0.23 g in NBW group and LBW group respectively. Fasting plasma ghrelin concentrations in UR group (1382 (1287–1513) pg/ml) were higher than that of NR group (1072 (974–1205) pg/ml). Plasma ghrelin concentrations in the LBW group (2176 (2031–2384) pg/ml) were significantly lower than that of the NBW group (2493 (2311–2675) pg/ml). Undernutrition caused a decrease in plasma insulin concentrations in both UR dams and LBW pups (P < 0.001). Ghrelin mRNA and total ghrelin of pancreas were significantly affected by intrauterine nutrition state. Pancreas insulin concentrations were significantly affected by intrauterine nutrition (P = 0.007). The majority of ghrelin-producing cells were present at the periphery of islets in the NBW group. Ghrelin was colocalized with insulin in ß-cells in LBW group. The percentage of ghrelin-positive cells in the islets of LBW group was significantly higher than that of the NBW group (P < 0.01). Intrauterine undernutrition may affect the birth weight, plasma insulin and ghrelin levels, islet ghrelin expression, and ghrelin cell distribution. It will be interesting to investigate intrauterine nutrition which is involved in islet ghrelin expression and ghrelin cell distribution.