Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on b-cell function and insulin sensitivity

Dietary protein restriction during pregnancy and lactation in rats impairs b-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores b-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of b-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation on b-cell function and insulin resistance in these offspring. Pregnant rats were fed i) control, ii) LP, and iii) LPCTau diets during gestation and lactation. Offspring were given a control diet following weaning. A fourth group consisting of offspring of LP-fed mothers, maintained on a LP diet following weaning, was also studied (LP-all life). Insulin sensitivity in the offspring of LP-fed mothers was reduced in females but not in males. In both genders, LP exposure decreased b-cell function. Tau supplementation improved insulin sensitivity in females and b-cell function in males. The LP-all life diet improved b-cell function in males. We conclude that i) maternal Tau supplementation has persistent effects on improving glucose metabolism (b-cell function and insulin sensitivity) in adult rat offspring of LP-fed mothers and ii) increasing the amount of protein in the diet of offspring adapted to a LP diet after weaning may impair glucose metabolism (b-cell function) in a gender-specific manner.Fil: Tang, Christine. University Of Toronto; Canadá;Fil: Marchand, K.elly. University of Western Ontario. Lawson Health Research Institute; Canadá;Fil: Lam, Loretta. University Of Toronto; Canadá;Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Thyssen, Sandra M.. University of Western Ontario. Lawson Health Research Institute; Canadá;Fil: Guo, June. University Of Toronto; Canadá;Fil: Giacca, A.dria. University Of Toronto; Canadá;Fil: Arany, Edith. University of Western Ontario. Lawson Health Research Institute; Canadá

The effects of low protein during gestation on mouse pancreatic development and beta cell regeneration

Beta cells are partially replaced in neonatal rodents after deletion with streptozotocin (STZ). Exposure of pregnant rats to a low protein (LP) diet impairs endocrine pancreas development in the offspring, leading to glucose intolerance in adulthood. Our objective was to determine whether protein restriction has a similar effect on the offspring in mice, and if this alters the capacity for beta cell regeneration after STZ. Pregnant Balb/c mice were fed a control (C) (20% protein) or an isocaloric LP (8% protein) diet during gestation. Pups were given 35 mg/kg STZ (or vehicle) from d 1 to 5 for each dietary treatment. Histologic analysis showed that C-fed offspring had largely replaced beta cell mass (BCM) after STZ by d 30, but this was not sustained over time. Female LP-fed offspring showed an initial increase in BCM by d 14 but developed glucose intolerance by d 130. In contrast, male LP offspring showed no changes in BCM or glucose tolerance. However, LP exposure limited the capacity for recovery of BCM in both genders after STZ treatment. Copyright © 2010 International Pediatric Research Foundation, Inc

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARa expression, lipid metabolism, lipoperoxidation, andnitricoxide(NO) productionare alteredinthe fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPARactivation on these parameters. We found decreased PPARa expression in the hearts ofmale but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARa ligand leukotriene B4upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with6%oliveoil or6%safflower oil,enrichedinunsaturatedfatty acids that canactivate PPARs, led to few changes in lipid concentrations, but up-regulated PPARa expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts ofmale fetuses in the diabetic group, was reduced by thematernal treatments supplementedwithsaffloweroil. In conclusion, impaired PPARa expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a genderdependent manner by treatments enriched with PPAR ligands

Acetone ingestion mimics a fasting state to improve glucose tolerance in a mouse model of gestational hyperglycemia

Gestational diabetes mellitus results, in part, from a sub‐optimal β‐cell mass (BCM) during pregnancy. Artemisinins were reported to increase BCM in models of diabetes by α‐ to β‐cell conversion leading to enhanced glucose tolerance. We used a mouse model of gestational glucose intolerance to compare the effects of an artemisinin (artesunate) on glycemia of pregnant mice with vehicle treatment (acetone) or no treatment. Animals were treated daily from gestational days (GD) 0.5 to 6.5. An intraperitoneal glucose tolerance test was performed prior to euthanasia at GD18.5 or post‐partum. Glucose tolerance was significantly improved in both pregnant and non‐pregnant mice with both artesunate and vehicle‐alone treatment, suggesting the outcome was primarily due to the acetone vehicle. In non‐pregnant, acetone‐treated animals, improved glucose tolerance was associated with a higher BCM and a significant increase in bihormonal insulin and glucagon‐con-taining pancreatic islet cells, suggesting α‐ to β‐cell conversion. BCM did not differ with treatment during pregnancy or post‐partum. However, placental weight was higher in acetone‐treated animals and was associated with an upregulation of apelinergic genes. Acetone‐treated animals had reduced weight gain during treatment despite comparable food consumption to non‐treated mice, suggesting transient effects on nutrient uptake. The mean duodenal and ileum villus height was reduced following exposure to acetone. We conclude that acetone treatment may mimic transient fasting, resulting in a subsequent improvement in glucose tolerance during pregnancy

Olive oil diet in mild pre-gestational diabetes impacts offspring β-cell development.

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect α and β cells in islets at post-natal day 2 and at 5 months of age. Morphometric analysis was carried out to determine the number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass. Moreover, this β-cell pancreatic deficit was prevented by the maternal supplementation with olive oil. While no changes in PPARα expression was detected in the pancreas, both PPARβ/δ and PPARγ expression were reduced in 5-month-old male offspring of diabetic rats. Interestingly, the reduction in PPAR β/δ expression was prevented by maternal olive-oil supplementation. To further explore the direct effects on PPARs, INS-1E (β) and αTC1-6 (α) cell lines were treated with oleic acid. Interestingly PPARβ/δ expression is highly expressed in INS-1E. Collectively, these findings suggest that olive oil supplementation in utero may prevent diabetes-induced β cell loss in postnatal life by modulating pancreatic PPARs

Addition of olive oil to diet of rats with mild pre-gestational diabetes impacts offspring β-cell development

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we demonstrated that maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study, we examined the effects of this diet on neonatal and adult pancreatic development in male and female offspring of mothers affected with pre-gestational diabetes. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy, these dams were fed a chow diet supplemented or not with 6% olive oil. Offspring pancreata was examined at day 2 and 5 months of age by immunohistochemistry followed by morphometric analysis to determine number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass that was prevented by maternal supplementation with olive oil. PPARα and PPARγ were localized mainly in α cells and PPARβ/δ in both α and β cells. Although Pparβ/δ and Pparγ RNA expression showed reduction in 5-month-old male offspring of diabetic rats, Pparβ/δ expression returned to control levels after olive-oil supplementation. Interestingly, in vitro exposure to oleic acid (major component of olive oil) and natural PPAR agonists such as LTB4, CPC and 15dPGJ2 also significantly increased expression of all Ppars in αTC1–6 cells. However, only oleic acid and 15dPGJ2 increased insulin and Pdx-1 expression in INS-1E cells suggesting a protective role in β-cells. Olive oil may be considered a dietary supplement to improve islet function in offspring of affected mothers with pre-gestational diabetes.Fil: Taqui, Bushra. Western University; CanadáFil: Asadi, Farzad. Western University; CanadáFil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Hardy, Daniel Barry. Western University; CanadáFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Arany, Edith Juliana. Western University; Canad