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. [Diabetologia (2002) 45:856-866] Keywords Rats, development, low protein diet, taurine, pancreatic islets, BrdU, TUNEL, IGF-II, Fas. . Poor nutrition in foetal and early life was reported to be detrimental to the development of the beta cell, and therefore could cause Type II diabetes [2,3]. We have described previously a model of protein deprivation where pregnant rats were fed either a control diet (C) containing 20% protein or an isocalorific low protein diet (LP) containing 8% protein throughout gestation. The mean body weight of LP pups was reduced at birth, and the structure and function of the foetal endocrine pancreas were altered [2,4]. The mean islet size was reduced after a low protein diet in association with a reduced rate of islet-cell proliferation, and a higher rate of apoptosis [2,5]. The islet expression of insulin-like growth factors (IGF-I and IGF-II), which protect against apoptosis while also Clinical epidemiological studies and animal studies, suggest that malnutrition in utero, even over a brief period, could cause irreversible changes in the offspring which could lead to Type II (non-insulindependent) diabetes mellitus, obesity, hypertension

In rats, an isoenergetic low protein diet (LP) given throughout gestation perturbs the development of the endocrine pancreas by reducing beta-cell mass and islet vascularization at birth. Taurine, an important amino acid during development, has been found to be low in fetal and maternal plasma. When added to a LP diet, taurine normalizes beta-cell mass. Therefore, we investigated the ability of taurine to correct altered islet vascularization. Rats were given 20% [control (C)] or 8% (LP) protein in the diet with or without supplementation with 25 g/L taurine (T) in drinking water (C+T and LP+T) during gestation and lactation. Immunostaining for vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1), a VEGF receptor, was performed on fetal and neonatal pancreatic sections. Blood vessel density and blood vessel number were analyzed morphometrically on semi-thin sections. Taurine supplementation restored a normal volume and numerical density of vessels in fetal islets. The number of cells showing immunoreactivity for VEGF and Flk-1 was reduced by 33 and 45%, respectively, in islet cells from LP fetuses. In 1-mo-old pups, VEGF-positive cells remained decreased by nearly 22%. Both VEGF and Flk-1 were restored in pancreatic endocrine cells of fetuses and pups given taurine. The LP diet induced a threefold overexpression of Flk-1 in ductal cells, which contain precursors of beta cells. However, taurine supplementation was without effect. In conclusion, underexpression of VEGF and Flk-1 is associated with the lower fetal islet vascularization induced by the maternal malnutrition. The addition of taurine to the maternal diet prevents such damage and has a potential role in islet vasculogenesis.

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