Neonatal rat dietary carbohydrate affects pancreatic islet insulin secretion in adults and progeny

Laychock, Suzanne G.; Vadlamudi, Satyaprasad; Patel, Mulchand S.

doi:10.1152/ajpendo.1995.269.4.e739

Cited by 22 publications

(19 citation statements)

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“…The metabolic phenotype (body weight, serum hormone levels, insulin secretory capacity of islets, and hypothalamic characteristics) of the HF rats during both the preweaning and postweaning periods was similar to that of the MF rats, which suggests that the development of the HC phenotype was not influenced by the artificial rearing technique employed in our studies (11,16,18,19,30,33,34). Because of the similarity in the phenotype of MF and HF rats, we used only MF rats as control in the present study.…”

Section: Methodsmentioning

confidence: 54%

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

Srinivasan

Mahmood

Patel

2013

American Journal of Physiology-Endocrinology and Metabolism

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Srinivasan M, Mahmood S, Patel MS. Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction. Am J Physiol Endocrinol Metab 304: E486 -E494, 2013. First published December 18, 2012 doi:10.1152/ajpendo.00519.2012.-Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/ PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats. obesity; hyperinsulinemia; calorie restriction by pair feeding; metabolic programing; suckling period IN THE PERIOD 2009 35.7% of the adult population in the US was classified as obese (BMI Ͼ30) (8). The presence of obesity significantly augments the risk for the onset of a number of metabolic disorders such as hypertension, adverse lipid concentrations, and type 2 diabetes (20). Epidemiological data and results from animal models indicate that altered nutritional experiences during early periods in life (fetal and suckling) can predispose the offspring for the development of obesity and metabolic diseases in later life via developmental programming effects (7). These early adaptations enable the organism to endure the nutritional stress but are detrimental in the long run.Developmental plasticity initiated during fetal development extends into the immediate postnatal period. For example, it has been shown that pancreatic islets and neurons are not fully mature at birth and that their development is completed in the immediate postnatal (suckling) period (10, 12). Hence, an encounter with an altered nutritional experie...

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Section: Methodsmentioning

confidence: 54%

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

Srinivasan

Mahmood

Patel

2013

American Journal of Physiology-Endocrinology and Metabolism

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“…The altered in vitro insulin secretory response of 2-HC fetal islets suggests increased responsiveness of these islets to these secretogogues. The increased insulin secretory response of fetal 2-HC islets to basal and high glucose is preserved in the immediate postweaning period (postnatal day 28) and in adulthood (16,25). Aberrations in islet functions that prime them for adult-onset disorders have been reported for fetuses of dams fed a low-protein diet and fetuses of a diabetic pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

Srinivasan¹,

Aalinkeel²,

Song³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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. Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. Am J Physiol Endocrinol Metab 290: E129 -E134, 2006. First published September 6, 2005 doi:10.1152/ajpendo.00248.2005We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adultonset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that malprogramming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny. maternal intrauterine environment; fetal programming; fetal hyperinsulinemia; obesity; pair feeding EPIDEMIOLOGICAL DATA AND RESULTS from animal models indicate that the nutritional status of the mother during pregnancy impacts on the expression of metabolic diseases in adulthood of the progeny (2,3,7,11,12,18,21,30). Extensive organ development continues to occur in the immediate postnatal life of the rat, suggesting that this period, too, is vulnerable for metabolic programming effects. Earlier, we showed that the overlap of an altered nutritional experience in the form of a high-carbohydrate (HC) milk formula with the critical window of postnatal organ development in neonatal rat pups resulted in the establishment of the HC phenotype (chronic hyperinsulinemia and adult-onset obesity) in these rats (19,26). Because of fetal development in HC female rats, adult progeny demonstrated the same HC phenotype (29). Whether the adaptations that predispose the progeny for expression of the HC phenotype in adult life occur during fetal development in the HC intrauterine environment was not explored in the earlier study.The suckling period in the rat ...

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“…1A). Alterations in the insulin secretory pathway observed in the neonatal HC islets are programmed into adult islets (31,32). The molecular changes (increase in the preproinsulin gene transcription) observed in islets from neonatal HC rats are also observed in adult HC islets (32).…”

Section: Programming Of Early Onset Adaptations Into Adulthoodmentioning

confidence: 92%

Metabolic Programming: Causes and Consequences

Patel

Srinivasan

2002

Journal of Biological Chemistry

114

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The normal programmed development of a multicellular organism from the germ cell is a synchronized series of events driven by genetic instructions acquired during conception. During the early critical periods in life the organism also has the ability to respond to environmental situations that are alien to normal development by adaptations at the cellular, molecular, and biochemical levels. Such early adaptations to a nutritional stress/stimulus permanently change the physiology and metabolism of the organism and continue to be expressed even in the absence of the stimulus/stress that initiated them, a process termed "metabolic programming" (1). A brief summary of the findings from human epidemiological and animal studies is presented below in support of the concept of metabolic programming induced by nutritional experiences during critical periods in development with consequences later in adulthood. For detailed accounts the reader is referred to excellent reviews on this subject (2-5). This minireview will focus on metabolic programming with reference to a novel rat model developed in our laboratory. Evidence for Metabolic Programming from Human Epidemiological DataExtensive epidemiological findings indicate that metabolic programming occurs in humans. Barker (6) was the first to suggest from epidemiological studies that the disproportionate size of the newborn resulting from maternal malnutrition correlated with an increased risk for adverse health outcomes (type II diabetes, hypertension, and cardiovascular diseases) later in adult life. These primary observations resulted in the now widely recognized "fetal origins" hypothesis emphasizing the importance of adequate maternal nutrition during pregnancy (4). Evidence for Metabolic Programming in AnimalsNutritional programming has been demonstrated in animal studies. In pioneering studies with rodents, McCance (7) demonstrated by adjusting litter size that the quantity of food consumed during early periods of postnatal life has long term consequences on growth. The consequences of maternal malnutrition induced by either a low protein diet or caloric restriction during gestation and lactation cause major changes in the structure and function of several organs in the offspring. Pregnant rats fed a low protein diet produced pups with alterations in pancreatic islets (8, 9). These include reduced islet vascularization, ␤ cell proliferative capacity, and islet size with rightward shift (decreased sensitivity) in glucose-stimulated insulin secretion and altered sensitivity to insulin in muscle (8, 9). Furthermore, hypothalamic nuclei are malformed in these weanling rats; this is accompanied by reduced vascularization of the cerebral cortex in the progeny (10). Metabolic capacities of the liver, muscle, and adipose tissue are compromised by maternal protein restriction during gestation and lactation with adverse adult onset outcomes (11). Elevated insulin concentrations during critical periods of development, as occurs perinatally in the offspring of gestationally dia...

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Neonatal rat dietary carbohydrate affects pancreatic islet insulin secretion in adults and progeny

Cited by 22 publications

References 9 publications

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

Metabolic Programming: Causes and Consequences

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