Effects Of Energy Restriction During Pregnancy On Islet ? Cells In Offspring Of Adult Rats

In agricultural production,due to insufficient feed supply or shortage of feed during pregnancy,it is easy to cause insufficient energy intake of the dam,resulting in intrauterine growth retardation?IUGR?.IUGR litter have lower birth weight and lower pancreas weight,and during the growth and development process after birth,it is easy to cause the lean meat quality of livestock to decline and lead to the occurrence of related metabolic diseases.At present,a variety of IUGR animal models indicate that insufficient maternal energy intake during pregnancy can result in impaired growth and development of islet beta cells and disordered insulin secretion in IUGR offspring.Including the area of?cells is reduced,the mass and number of?cells are decreased,insulin secretion is decreased,and the expression level of PDX-1?pancreatic duodenal homeobox factor-1?is decreased.However,most of the IUGR restricted feeding models are studied primarily during maternal pregnancy and lactation,and are concentrated in the islet beta cells of the fetus and newborn.Therefore,it is unclear whether the islet injury caused by fetal energy restriction can be restored to a certain extent by the compensation of normal diet after birth.In other words,whether the IUGR progeny restores normal energy intake after birth has a persistent effect on islet?cells and related regulatory mechanisms remain to be studied.Therefore,in this study,Sprague Dawley?SD?rats were used as experimental materials to investigate the effects of normal energy intake on the islet?cell morphology and insulin secretion function of IUGR offspring after birth.This study aims to provide a theoretical basis for exploring the effects of restoring normal energy intake of IUGR offspring after birth on adult offspring-related metabolic diseases and related regulatory mechanisms.The test content is mainly divided into three parts:First,the IUGR rat model was established by limiting the 50%intake of feed during the 10th day of pregnancy to the time of delivery,while the IUGR rat were fed normal energy during the lactation period to 12 weeks of age?IUGR group?;In the control group,the offspring were fed normal energy during the gestation period to 12weeks of age?Control group?.Second,through the intraperitoneal injection of glucose tolerance test?IPGTT?,the glucose tolerance and insulin secretion response function of 12-week-old rats were tested at the overall level;Primary islet cells of 12-week-old rats were extracted,and mRNA expression changes of insulin secretion-related regulatory factors such as glucose transport,K_ATPTP channel,Ca²⁺channel and insulin gene were analyzed by RT-qPCR.Third,morphological analysis of islet?cells in 12-week-old rats by immunohistochemistry;RT-qPCR was used to analyze the expression changes of islet growth and development related factors such as PDX-1,IGFs,FGFs,EGF and VEGFa in primary islet cells of 12-week-old rats.The results of this test:First,the birth weight of the offspring of the IUGR group?0 weeks?was 12.7%lower than that of the Control group?P<0.01?,while the weekly weight before the 12weeks of age was not different between the IUGR group and the Control group.There was no difference in the weight changes of tissues?eg,pancreas,liver,spleen,heart,and lung?of 12-week-old offspring rats.Second,the IPGTT test found that there was no difference in blood glucose concentration changes in the 12-week-old offspring rats,but the plasma insulin concentrations in the IUGR group decreased at 60 min and 120 min?P<0.05?.RT-qPCR results showed that there was no significant difference in mRNA expression of insulin secretion-related regulatory factors?GLUT2,Kir6.2,CACNA1C,MICU1,PPAR?,PPAR?,UCP2,Insulin1,Insulin2,and IR?.Third,Immunofluorescence staining showed that the islet?cell diffuse distribution between the pancreatic exocrine acinar tissues;After statistical analysis,there was no significant difference in the area of islet?cells and the ratio of pancreatic tissue area.RT-RCR results showed that except for the up-regulation of PDX-1expression in the IUGR group?P<0.05?,there were no significant differences in mRNA expression of other islet cell growth and development related regulatory factors?IGFs,FGF10,FGF21,FGFR1,FGFR2,EGF,EGFR and VEGFa?.According to the above results,it can be inferred that:First,the IUGR rat model was successfully constructed during pregnancy using a50%restriction.In addition,IUGR rat can catch up with body weight by restoring normal energy intake after birth,and return the body weight and pancreas weight of adult offspring rats to normal levels.Second,through the insulin secretion response test,it was found that the blood glucose concentration of the IUGR group did not change and the plasma insulin concentration decreased,indicating that the IUGR rat have the potential for enhanced insulin sensitivity after adulthood.Third,there was no significant difference in the islet?cell area and the ratio of pancreatic area to the adult rat,indicating that the normal energy intake of the IUGR rat can restore the growth and development of islet?cells to normal levels,and the up-regulated expression of PDX-1 can explain this compensation mechanism.In summary:Maternal gestational energy restriction produces low birth weight IUGR rat,but normal energy intake after birth of IUGR offspring can restore the body weight,pancreas weight,islet?cell area and insulin secretion response function of adult offspring rats to normal levels.Although the up-regulated PDX-1 signal in islet beta cells acts as a potential compensatory mechanism to restore islet damage caused by congenital energy restriction,persistent PDX-1 up-regulation accompanied by increased insulin sensitivity in peripheral tissues is also more likely to lead to excessive proliferation of islet?-cells after birth and metabolic diseases such as obesity.