Effects And Mechanisms Of Taurine Supplementation On Islet Remodeling Of Low Birth Weight Neonatal Rat

BackgroundRecently epidemiological investigations and experimental animalstudies had suggested that low birth weight was not only one of theimportant reasons of death and illness of perinatal baby, but also adangerous factor of metabolic syndrome (MS) during adulthood such ashypertension and diabetes mellitus. Therefore it was a heat topic to studythe mechanisms of low birth weight and MS and to find an effectivemeasure to prevent and treat MS. Many organs and tissues in perinataldevelopment must experience remodeling, including dynamic changes ofproliferation, apoptosis and differentiation. It was proved that the periodof fetal and postnatal 21-day was the pivotal phase of islet remodeling,and after this phase, the function and structure of islet had been"programmed", which would product lifetime effect on the homeostasisof blood sugar. During the pivotal phase, islet development was sensitiveto malnutrition, and malnutrition would damage the function andstructure of islet. Taurine, as an important essential amino acid duringdevelopment, had been found to be low in low birth weight baby. Taurinehad the insulin-like effect and participated in the regulation of bloodsugar. Moreover as an endogenisis protection, taurine can protect thefunction ofβcell. Taurine can improve the proliferation anddifferentiation of neural cell, and can restrain the apoptosis . But therewas little study of taurine and islet remodeling.Objective(1) To observe the newborn member per nest, body weight ofneonatal rat, IUGR rate and perinatal death rate of neonatal rat when thepregnant rates were fed 10％low protein diet or 21％normal protein diet; and to test whether feeding pregnant rates 10％low protein diet was aneffective method to making low birth we'ight neonatal rat model. (2) Toobserve the changes of body weight, blood sugar levels, plasma insulinlevels, BCM and ultrastructure of islet 13 cell in the low birth weightneonatal rats during early postnatal life. (3) To study the effects andmechanisms of taurine on islet remodeling of low birth weight neonatalrat from proliferation, apoptosis and differentiation points of view.Methods(1) The building of low birth weight neonatal rat model andgroups: forty male and forty female healthy three-month SD rates wereborght. Male and female rats were put into a cage at the proportion of 1:1.The pregnant rats were divided into four group:①the model of low birthweight neonatal rats was made by feeding 10％low protein diet to thepregnant rats of group R (R) during gestation and lactation;②feeding 21％normal protein diet to the pregnant rats in control group (C);③a partof group R were given a supplementation with 2.5％taurine drinkingwater (RT) only during 21-day lactation;④and a part of group C weregiven a a supplementation with 2.5％taurine drinking water (CT)onlyduring 21-day lactation. Other femal rats were given running warter. Toobserve the neobom member per nest, body weight of neonatal rat, IUGRrate and perinatal death rate in group R and C.(2) Changes of islet function and structure: At postnatal day1, 7, 14 and 21, the neonatal rats were weighted and their pancreas wereremoved.①Blood was collected for detecting blood sugar and plasmainsulin levels.②Expression of insulin protein was detected by immuno-histochemical staining technique in pancreas slices, and calculated theβcell mass (BCM): BCM (mg)=insulin-positive area/total pancreas area×pancreas weight.③The ultrastructural changes ofβcell wereobserved by electron microscopy.(3) Detecting factors about islet remodeling:①Expression ofBrdU was detected by immuno- histochemical staining techniqe in pancreas slices, and the degree of proliferation was assessed throughproliferation index (PI).②Apoptotic cells were detected by theTdT-mediated dUTP-biotin nick end -labeling technique (TUNEL) inpancreas slices, and the degree of apoptosis was assessed throughapoptosis index (AI)③Insulin and PDX-1 mRNA expression inpancreas tissue were evaluated by RT-PCR. All data were statisticedwith the SPSS-11.0; differences between groups were evaluated usingLSD method in One-Way AVOVA and P value＜0.05 was consideredsignificant.Results(1) The building of low birth weight neonatal rat model: theoffspring in group R got low birth weight and more offspring can becalled IUGR rat. But there was no obvious changes in the neobornmember per nest and perinatal death rate between group R and C.(2) Changes of islet function and structure:①The levels ofblood sugar and plasma insulin had no significant difference betweenevery group of every age.②BCM in each group increased with aging,and BCM in group R was lower than in group C.③At postnatal day 1,the quantity ofβcell in group R was less than in group C and thestructure of endocrinal grains inβcell was not integrate and distributionof those was not symmetrical. At postnatal day 21, the size anddistribution of endocrinal grains inβcell were less symmetrical in groupR than in group C, and more pale-granules and degranulations ofβcellwere found in group R than in group C.(3) Detecting factors about islet remodeling:①During thepostnatal 21-day, the body weight of offspring in group RT was slightlyhigher than that in group R.②At postnatal day 21, the size anddistribution of endocrinal grains inβcell were more symmetrical in groupRT than in group R. And less pale-granules and degranulations ofβcellwere found in group RT than in group R, but the ultrastructure in groupRT did not resume the configuration in group C.③Insulin mRNA expression and BCM in every group increased with aging; and insulinmRNA expression and BCM in group RT were higher than in group R,closed to the levels in group C and CT.④The PI of islet cells in everygroups decreased with aging. The PI in group RT was higher than ingroup R and closed to the levels in group C and CT.⑤The AI of isletcells in every groups experienced a dynamic change during the postnatal21-day. The AI in group RT was lower than in group R, but higher thanin group C and CT.⑥PDX-lmRNA expression in every group decreasedwith aging and PDX-1 mRNA expression in group RT were higher thanin group R, closed to the levels in group C and CT.Conclusion(1) Feeding 10％low protein diet to the pregnant rat was aneffective method to make low birth weight neonatal rat model. (2)During the postnatal 21 days, the blood sugar and plasma insulinremained normal levels in low birth weigh neonatal rats; but the isletstructure had been damaged, which included decreased BCM anddamaged ultrastructure ofβcell. (3) Taurine supplementation during thepostnatal 21-day can slightly improve the growth-catch-up, and can slowdown the decreasing tendency of proliferation, decrease the apoptosisand increase the differentiation of islet cell. As a result, taurine increasedtheβcell mass of low birth weight neonatal rats and improve the isletremodeling.