Islet Function in Offspring of Mothers on Low-Protein Diet During Gestation

Dahri, S.; Snoeck, A.; Reusens-Billen, B; Remacle, Claude; Jj, Hoet

doi:10.2337/diab.40.2.s115

Cited by 414 publications

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“…The early period (days 0-7) corresponds to the embryonic phase of development in the rat and in fact embryos only implant at around day 4.5. 7 The mid-gestation period (days [8][9][10][11][12][13][14] largely corresponds to the period of organogenesis, while late gestation (days [15][16][17][18][19][20][21][22] is the period of most rapid growth and differentiation of key structures. By feeding at these targeted periods, it is possible to identify when nutritional programming occurs and this can provide important indicators of potential mechanisms.…”

Section: Animalsmentioning

confidence: 99%

“…A large number of studies in rats, mice, guinea pigs and sheep have clearly shown that exposure to relatively short periods of undernutrition or endocrine disturbance in fetal life can programme raised blood pressure, glucose intolerance and insulin resistance. [7][8][9] The range of nutritional exposures capable of eliciting programmed responses in the developing offspring is broad, including micronutrient deficiency, [10][11][12] excess of saturated fat 13 and restriction of food intake (global nutrient restriction). 14,15 In the present paper, we report findings from a model of low protein feeding in rat pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

2006

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Objective: To assess the long-term impact of undernutrition during specific periods of fetal life, upon central adiposity, control of feeding behaviour and locomotor activity. Design: Pregnant rats were fed a control or low-protein (LP) diet, targeted to early (LPE), mid (LPM) or late (LPL) pregnancy or throughout gestation (LPA). The offspring were studied at 9 and 18 months of age. Measurements: Adiposity was assessed by measuring weight of abdominal fat depots relative to body weight. Locomotor activity was assessed using an infrared sensor array system in both light and dark conditions. Hypothalamic expression of mRNA for galanin and the galanin 2 receptor (Gal2R) was determined using real-time PCR. Results: At 9 months, male rats exposed to LP in utero had less fat in the gonadal depot, but were of similar body weight to controls. By 18 months, the males of groups LPA and LPM had more abdominal and less subcutaneous fat. Females deposited more fat centrally than males between 9 and 18 months of age, and this was more marked in groups LPA and LPL. Food intake was greater in LPM males. Among females hypophagia was noted in groups LPA and LPL. Expression of galanin and Gal2R were unaffected by maternal diet. Total locomotor activity was reduced in LPE males and all LP females in the light but not in the dark. Conclusion: Locomotor activity and feeding behaviour in aged rats are subject to prenatal programming influences. Fetal undernutrition does not programme obesity in rats without postnatal dietary challenge.

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Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

2006

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“…A recent review study suggested that inadequate maternal nutrition might disturb the development of the fetus, which must adopt strategies to ensure survival that will programme its future health [3]. In experimental animal models, alteration of the intrauterine environment induced, for example, by gestational diabetes [4], placental insufficiency [5,6] or poor maternal nutrition [7][8][9][10][11] compromise the development of endocrine pancreas in the progeny and impact on its future health even in the subsequent generation [4,6,12]. Reduction of food intake by 50% in rats during gestation reduced the beta cell mass in offspring at birth by 30% [9].…”

Section: Introductionmentioning

confidence: 99%

“…When maternal diet was reduced in protein content during gestation, a number of findings were observed: reduction in beta cell mass due to diminished proliferation [8,13], enhanced apoptosis [11,13], reduced insulin secretion in vitro from isolated islets [14], impaired islet vascularisation [8,15] and enhanced sensitivity to cytotoxic effects of cytokines in vitro [11]. Increased susceptibility to cytokine cytotoxicity and lower insulin secretion persisted in adulthood despite limiting the low-protein (LP) diet to the period of gestation and lactation [7,12]. Maternal and fetal plasma glucose levels were not altered by maternal malnutrition, but the plasma amino acid profile was perturbed both in the mother and their fetuses [16].…”

Section: Introductionmentioning

confidence: 99%

The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

et al. 2008

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Aims/hypothesis Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes. Methods Pregnant Wistar rats were fed an LP diet (8% [wt/wt] protein) supplemented or not with taurine in the drinking water or a control diet (20% [wt/wt] protein). At 21.5 days of gestation, fetal pancreases were removed, digested and cultured for 7 days. Neoformed islets were collected and transcriptome analysis was performed. Results Maternal LP diet significantly changed the expression of more than 10% of the genes. Tricarboxylic acid cycle and ATP production were highly targeted, but so too were cell proliferation and defence. Maternal taurine supplementation normalised the expression of all altered genes. Conclusions/interpretation Development of the beta cells and particularly their respiration is modulated by the intrauterine environment, which may epigenetically modify expression of the genome and programme the beta cell towards a pre-diabetic phenotype. This mis-programming by maternal LP diet was prevented by early taurine intervention.Keywords Diabetes . Early programming . Fetal islets . Maternal low-protein diet . Rats . Taurine . Transcriptome Abbreviations EST expressed sequence tag LP low protein LPT low-protein diet supplemented with taurine SAM significance analysis of microarrays TCA tricarboxylic acid Diabetologia (2008) 51:836-845

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“…In this model, a low-protein (LP) diet (8% vs 20% control) given during gestation leads to offspring having lower body weight. Pancreatic beta cell mass, insulin content and insulin secretion are reduced at birth [2,3]. In addition, in vivo and in vitro, the proliferation rate of fetal islet cells is lower [2,4,5,6], while apoptosis is higher [5,6,7].…”

Section: Introductionmentioning

confidence: 99%

Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines

et al. 2004

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Aims/hypothesis. A maternal low-protein diet has been shown to induce an increased susceptibility of fetal islets to cytokines, but this effect can be avoided by maternal taurine supplementation. Here, we question whether these effects persist until adulthood in the offspring, despite the animal having a normal diet after weaning. Methods. Pregnant Wistar rats received a diet of either 20% or 8% protein (control [C group] and recuperated [R group] respectively), which was or was not supplemented with taurine (control treated with taurine [CT group] and recuperated treated with taurine [RT group] respectively) during gestation and lactation. When the female offspring reached adulthood, an OGTT was performed. In a second stage, islets were isolated from these offspring, then pretreated or not with taurine, and subsequently treated with cytokines. Results. Fasting glycaemia was higher (p<0.05) and insulinaemia was lower (p<0.01) in the R group than in the C group. Taurine supplementation decreased insulinaemia in the CT group and tended to increase it in the RT group. After the OGTT, glycaemia in R animals was not different from that in the C group, despite a blunted insulin response (p<0.05) which was restored by taurine. Supplementation in C-group mothers led to a weak glucose intolerance. In vitro, more apoptotic cells were observed in R islets after cytokines treatment (p<0.01). The addition of taurine to the culture medium in the R and C groups protected the islets from the cytokines (p<0.01). Maternal taurine supplementation decreased the sensitivity of islets in the RT group (p<0.01), but increased sensitivity in the CT group (p<0.01). Conclusions/interpretation. The increased vulnerability of islets to cytokines due to a restriction of protein during fetal development was still evident when the offspring reached adulthood. The low-protein diet also induced hyperglycaemia in the presence of lower insulinaemia. Taurine supplementation protected adult islets of the R group from cytokine toxicity and restored the insulinaemia. However, unnecessary supplementation of taurine could have detrimental effects.

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Islet Function in Offspring of Mothers on Low-Protein Diet During Gestation

Cited by 414 publications

References 0 publications

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines

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