Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice.

AIMS/HYPOTHESIS: We hypothesised that nutritional taurine, which is important for the development of the endocrine pancreas and reduces cytokine-induced apoptosis in pancreatic beta cells, would prevent or delay the onset of autoimmune diabetes, if given early in life to the non-obese diabetic (NOD) mouse. METHODS: Pregnant NOD mice received a diet supplemented with taurine throughout gestation or until weaning, and the pancreas of the offspring was examined using immunohistochemistry. This was done at postnatal day 14 and after 8 weeks (assessment of insulitis). The animals were also monitored until they became diabetic. RESULTS: At 14 days, pancreatic islet mass was significantly greater in animals treated with taurine than in controls. This finding was associated with a greater incidence of islet cell proliferation and a lower incidence of apoptosis. At age 8 weeks the number of islets manifesting insulitis was reduced by more than half, and the area of insulitis was reduced by 90%. Taurine treatment delayed the mean onset time of diabetes from 18 to 30 weeks in females, and from 30 to 38 weeks in males, while 20% of treated females remained free of diabetes after one year. CONCLUSIONS/INTERPRETATION: Taurine supplementation in early life altered islet development, reduced insulitis and delayed the onset of diabetes in NOD mice.

Low-protein diet during early life causes a reduction in the frequency of cells immunopositive for nestin and CD34 in both pancreatic ducts and islets in the rat.

Feeding a low-protein (LP) diet to pregnant and lactating rats impairs pancreatic islet mass and insulin release in the offspring, leading to glucose intolerance as adults. We hypothesized that an LP diet changes the number of pancreatic endocrine precursor cells or cells supporting endocrine cell neogenesis. Pregnant rats were given LP (8% protein) or a control (20% protein) diet from conception until postnatal d 21. Cells containing nestin, CD34, or c-Kit were quantified in pancreata of the offspring. Stellate cells immunoreactive for nestin were seen to be adjacent to ductal epithelium and were resident within the islets. These were proliferative and immunonegative for cytokeratin 20, fibronectin, tyrosine hydroxylase, pancreatic duodenal homeobox 1, Nk homeodomain transcription factor 6.1, or insulin, but expressed vimentin. Approximately 20% of islet nestin-positive cells also expressed the endothelial cell marker platelet endothelial cell adhesion molecule-1. Both ducts and islets also contained CD34- and c-Kit-positive cells with similar morphology to those expressing nestin. Offspring from rats fed the LP diet had significantly less nestin/CD34-positive cells and reduced expression of nestin mRNA. Within islets, there was an associated decrease in cell proliferation and in cells immunopositive for pancreatic duodenal homeobox 1. Nestin-positive cell number within islets correlated positively with the percent area of beta-cells. Supplementation of pregnant and lactating rats with taurine reversed the deficits in mean islet area and nestin-positive cells caused by the LP diet within the islets of the offspring. Nutritional programming of postnatal beta-cell mass may involve an altered abundance of cells expressing nestin and/or CD34, which may limit endocrine cell development.

Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets.

AIMS/HYPOTHESIS: In our previous studies a low protein diet (8% vs 20%) given during foetal and early postnatal life induced abnormal development of the endocrine pancreas; beta-cell mass and islet-cell proliferation were reduced while apoptosis was increased. Taurine, an important amino acid for development was also reduced in maternal and foetal plasma of protein deficient animals. In this study we aim to evaluate the role of taurine in the alterations observed in rats after a low protein diet. METHODS: Four groups of rats were given either a control, a low protein, or control and low protein diets with 2.5% taurine in the drinking water. Diets were given to gestating and lactating mothers and to their pups until day 30. Beta and endocrine cell masses were analysed as well as DNA synthesis and apoptosis after taurine supplementation in foetuses and pups. We also investigated insulin like growth factor-II (IGF-II), inducible nitric oxide synthase (iNOS), and Fas by immunohistochemistry. RESULTS: In foetuses and neonates nourished with a low protein diet, taurine supplementation restored normal DNA synthesis and apoptosis. This led to adequate beta and endocrine cell mass in pups. In islet cells, immunoreactivity was increased for IGF-II, reduced for Fas and unchanged for iNOS after taurine supplementation. CONCLUSION/INTERPRETATION: Taurine supplementation to a low protein diet in foetal and early postnatal life prevents the abnormal development of the endocrine pancreas. The mechanisms by which taurine acts on DNA synthesis and apoptosis rate of endocrine cells involve IGF-II, Fas regulation but not iNOS.