Nutritional influences on pancreatic development and potential links with non-insulin-dependent diabetes

Dahri, S.; Reusens, Brigitte; Remacle, Claude; Hoet, J. J.

doi:10.1079/pns19950003

Cited by 113 publications

(85 citation statements)

References 27 publications

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“…Past work has suggested that diets containing lower protein concentration than those with adequate nutrition resulted in decreased pancreatic insulin concentration (Dahri et al, 1995). Other studies have suggested that the β-cell proportional area (relative to total cellular area) and islet number was decreased in rats undergoing nutrient restriction for a period of 4 weeks when compared with a control group fed for ad libitum intake (Chen et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Keomanivong

Lemley

Camacho

et al. 2016

Animal

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Primiparous ewes ( n = 32) were assigned to dietary treatments in a 2 × 2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased ( P ⩽ 0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass ( P = 0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased ( P = 0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster ( P = 0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area ( P = 0.03) and percent of large (32 001 to 512 000 µm 2 ) and giant (⩾512 001 µm 2 ) insulin-containing cell clusters ( P = 0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater ( P ⩽ 0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm 2 ) while fetuses had more ( P < 0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters ( P ⩽ 0.02). Larger insulin-containing clusters were observed in fetuses ( P < 0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased α-amylase content. Nutrient restriction decreased the number of pancreatic insulin-containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial.Keywords: development, ewes, melatonin, nutrient restriction, pancreas ImplicationsMelatonin is a potential therapeutic to overcome negative effects of nutrient restriction during pregnancy because of its roles in regulating blood flow and gastr...

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Section: Discussionmentioning

confidence: 99%

“…Developmental changes in islet size and number potentially could have effects on development in regards to energetics and function of β-cells. When investigating islet size of the endocrine pancreas, pups borne from mothers fed low protein diets were found to have islet cell proliferation reduced by 12% (Dahri et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Keomanivong

Lemley

Camacho

et al. 2016

Animal

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“…15 Despite feeding the animals with a normal diet after weaning, the adult offspring showed a lower plasma insulin level and insulin secretion after glucose challenge. 16 A maternal low protein diet also induced changes in zonation and enzyme activity in the liver of the pups that was not restored at adulthood even when the animals were fed a normal diet. An increased sensitivity of peripheral organs to insulin was observed in young adulthood, but which deteriorated, and the insulin resistance appeared in later life.…”

Section: The Programming Of the Metabolic Syndromementioning

confidence: 99%

Programming of obesity and cardiovascular disease

2004

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BACKGROUND: There is evidence that malnutrition in early life induces a growth retardation leading, in adult life, to manifest components of the metabolic syndrome. However, the impact on obesity seems less clearly established. OBJECTIVE: To review the effects of foetal and postnatal malnutrition on the programming of obesity in the context of the metabolic syndrome, as well as the link between central obesity and cardiovascular diseases. METHODS: Included in the review were recent papers exploring the mechanisms linking maternal nutrition with impaired foetal growth and later obesity, cardiovascular disease, hypertension and diabetes in humans and animals. RESULTS: The programming of obesity during foetal and early postnatal life depends of the timing of maternal malnutrition as well as the postnatal environment. Obesity arises principally in offspring submitted to malnutrition during early stages of gestation and which presented early catch-up growth. The programming may involve the dysregulation of appetite control or the hormonal environment leading to a context favourable to obesity development (hypersecretion of corticosteroids, hyperinsulinaemia and hyperleptinaemia and anomalies in the IGF axis). Adipose tissue secretes actively several factors implicated in inflammation, blood pressure, coagulation and fibrinolysis. The programmed development of intra-abdominal obesity after early growth restriction may thus favour higher prevalence of hypertension and cardiovascular diseases. CONCLUSIONS: Abdominal obesity appears in malnourished offspring and is aggravated by early catch-up growth. Higher rates of intra-abdominal obesity observed after growth restriction may participate to hypertension and create atherothrombotic conditions leading to the development of cardiovascular diseases.

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“…Fetal LP islets exposed to interleukin-1β (IL-1β) or to nitric oxide (NO · ) donor, toxic molecules implicated in beta cell damage in Type 1 diabetes, are more sensitive than control islets, showing that an LP diet in fetal and early life increases the vulnerability of fetal islets. Resuming a normal diet after birth or after weaning does not restore a normal plasma insulin level in the offspring, which is reduced in fasting state and after an oral glucose challenge in adulthood [8,9].…”

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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Nutritional influences on pancreatic development and potential links with non-insulin-dependent diabetes

Cited by 113 publications

References 27 publications

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

Programming of obesity and cardiovascular disease

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

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