Biomedical subjects

R Aalinkeel

Publications and source records attributed to R Aalinkeel.

10 recordsLinked to original sources

PubMed2006

Endocrine regulation in asymmetric intrauterine fetal growth retardation.

OBJECTIVE: The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother. MATERIALS AND METHODS: We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA). RESULTS: (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers. CONCLUSION: Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary-thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.

Adult↗

PubMed2005

Thyroid hormone dysregulation in intrauterine growth retardation associated with maternal malnutrition and/or anemia.

Data on the effect of maternal malnutrition and/or anemia on thyroid hormone regulation in human fetuses are scarce, and would be of great importance in examining the relevance of Barker's hypothesis, which proposes adaptation of fetuses to undernutrition leading to permanent metabolic and endocrine changes that form the basis of adult diseases. To examine the quantitative variations in thyroid hormone profile of neonates born to malnourished and/or anemic mothers, we quantitated the T3, T4, rT3 and TSH levels in cord blood of neonates and maternal blood of their corresponding mothers that are malnourished and/or anemic. Further, we classified neonates born to each of these groups of mothers into Small for Gestational Age (SGA) or Appropriate for Gestational Age (AGA) based on the intrauterine growth curve for our population, and examined the thyroid hormone profile in these neonates. Our results show that firstly, the effects of malnutrition or anemia on thyroid hormone profile are distinct, secondly, significantly higher levels of cord blood T4 and correspondingly lower levels of T3 and rT3 are observed in the neonates born to anemic and malnourished mothers and thirdly, decreases in cord blood T3 levels were observed in Small for Gestational Age neonates born to anemic mothers. These observations lead us to speculate that alterations in the pituitary-thyroid function result in beneficial adaptations to the hostile intrauterine environment in malnutrition related growth retardation and anemia.

Anemia↗

PubMed2001

Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula.

Four day-old rat pups artificially raised on a high carbohydrate (HC) milk formula during their suckling period immediately develop hyperinsulinemia which persists into adulthood despite weaning onto lab chow on day 24. The present study investigates the molecular adaptations in islets isolated from neonatal rats in response to this dietary treatment during their suckling period. There is a significant increase in the level of preproinsulin mRNA and insulin biosynthesis in 12 day-old HC islets compared to islets from age-matched mother-fed (MF) control rats. Pancreatic duodenal homeobox factor-1 (PDX-1) modulates pancreatic ontogeny as well as preproinsulin gene expression in islets from neonatal rats. The mRNA level, DNA binding activity and protein content of PDX-1 are significantly increased in HC islets. The stress-activated protein kinase-2 and phosphatidylinositol 3-kinase have been reported to modulate PDX-1 activity in islets. The mRNA levels of these kinases are increased in HC islets. The mRNA level of upstream stimulatory factor (a modulator of PDX-1 gene expression) is also significantly increased in HC islets. These results indicate that the upregulation of several molecular events, including increases in the gene expression of preproinsulin, transcription factors and kinases may contribute to the chronic hyperinsulinemic state in the HC rats.

Journal Article↗

PubMed2001

Mitochondrial-encoded gene regulation in rat pancreatic islets.

Mitochondrial adenosine triphosphate (ATP) generation plays a major role in insulin secretion in pancreatic islet beta cells. The relationship between age and nutritional status of the islet and mitochondrial gene messenger RNA (mRNA) expression was investigated. Three animal groups were studied: infant (12-day-old) rats fed either mother's milk or a high carbohydrate (HC) diet; young (2 to 4-month-old) rats; and old (12 to 14-month-old) rats. The expression of mitochondrial cytochrome oxidase (CYO) (subunits I, II, and III), beta-nicotinamide adenine dinucleotide, reduced form dehydrogenase subunit 4 (NADH-DH4), and ATP synthase (subunit 6) (ATP-SYN6) mRNAs was characterized by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The mitochondrial gene mRNAs were identified in each of the groups of rat islets and in RINm5F cells. CYO-II mRNA expression in young and old rat pancreatic islets was 12.7- and 8.2-fold higher, respectively, compared with the level in infant rat islets. The expression of NADH-DH4 and ATP-SYN6 mRNAs was 47% and 40% lower, respectively, in young rat islets compared with the level in infant rat islets. CYO-I, CYO-III, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GPDH) mRNA expression did not differ between experimental groups. Artificial rearing of infant rat pups on a HC diet for 8 days lead to a 3.3-fold increase in islet CYO-II mRNA expression compared with mother-fed pups. However, glucose (11 mmol/L) stimulation of cultured isolated islets from young and old rats for 4 days failed to affect the expression level of mitochondrial gene mRNAs. Thus, aging affected the differential expression of CYO-II, NADH-DH4, and ATP-SYN6 mRNAs in rat islets. CYO-II mRNA expression was modulated only in infant rat islets after in vivo administration of carbohydrate.

Aging↗

PubMed2001

Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.

To investigate the influence of a high carbohydrate (HC) intake during the suckling period on pancreatic function in adult life, neonatal rats were artificially reared on a HC milk formula during the preweaning period and then weaned onto lab chow. In the adult HC rat, hyperinsulinemia is sustained by a variety of biochemical and molecular adaptations induced in the HC islets during the suckling period. The adult HC islets showed a distinct left shift in the glucose-stimulated insulin-secretory pattern. HC islets were also able to secrete moderate levels of insulin in the absence of glucose and in the presence of Ca(2+) channel inhibitors. In addition, the mRNA levels of preproinsulin, somatostatin transcription factor-1, upstream stimulatory factor-1, stress-activated protein kinase-2, phosphatidylinositol kinase, and GLUT-2 genes were significantly increased in HC islets. These results show that consumption of a HC formula during the suckling period programs pancreatic islet function in adult rats, resulting in the maintenance of hyperinsulinemia in the postweaning period and eventually leading to the development of obesity in adult life.

Animals↗

PubMed2001

A long-term high-carbohydrate diet causes an altered ontogeny of pancreatic islets of Langerhans in the neonatal rat.

Neonatal rats fed a high-carbohydrate (HC) formula by gastrostomy are hyperinsulinemic but normoglycemic. We determined whether HC formula altered pancreatic islet cell ontogeny. Rats were reared from d 4 on an HC formula or a high-fat formula, or were allowed to suckle naturally, and the pancreata were examined histologically from animals < or =24 d of age. The mean area of individual islets was reduced, but islet number was increased in HC rats compared with mother-fed or high fat-fed animals, which were similar. Islets from HC animals were relatively deficient in alpha cells and had a greater incidence of islet cells with fragmented DNA, indicative of apoptosis. Ductal epithelium, a source of new islets by neogenesis, had a greater incidence of cells staining immunopositive for proliferating cell nuclear antigen, a marker of cell replication, and a lower incidence of apoptosis. The islet cell mitogen and survival factor, IGF-II, had a reduced mRNA expression in whole pancreas from HC animals. The relative area of islet cells demonstrating IGF-II immunoreactivity was reduced in HC-fed rats versus controls, although a greater percentage of ductal epithelial cells were immunopositive. HC formula alters islet cell ontogeny by affecting islet size and number, which may be linked to an altered IGF-II expression.

Animals↗

PubMed2001

Use of a cDNA array for the identification of genes induced in islets of suckling rats by a high-carbohydrate nutritional intervention.

Four-day-old rat pups that are raised artificially on a high-carbohydrate (HC) milk formula immediately develop hyperinsulinemia, which persists into adulthood without any further nutritional stimulus. cDNA array analysis was used to identify large-scale changes in gene expression patterns in islets from 12- and 100-day-old HC rats in response to the HC dietary modification during the suckling period. It was observed that the expression of several genes that belong to clusters involved in beta-cell development and/or beta-cell function was significantly upregulated in islets from 12- and 100-day-old HC rats. It is inferred that in addition to predicted changes in gene expression, for example preproinsulin gene, global changes in gene expression contribute to the hyperinsulinemic state in the HC rat.

Aging↗

PubMed2000

Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula.

Artificial rearing of neonatal rats on a high-carbohydrate (HC) milk formula resulted in the immediate onset of hyperinsulinemia. This study examines, in islets of 12-day-old HC rats, adaptive changes that support the hyperinsulinemic state. Increases in plasma glucagon-like peptide-1 (GLP-1) levels and islet GLP-1 receptor mRNA supported increased insulin secretion by HC islets. Isolated HC islets, but not mother-fed (MF) islets, secreted moderate amounts of insulin in a glucose- and Ca(2+)-independent manner. Under stringent Ca(2+)-free conditions and in the presence of glucose, GLP-1 plus acetylcholine augmented insulin release to a larger extent in HC islets. Levels of adenylyl cyclase type VI mRNA and activities of protein kinase A, protein kinase C, and calcium calmodulin kinase II were increased in HC islets. A tenfold increase in norepinephrine concentration was required to inhibit insulin secretion in HC islets compared with MF islets, indicating reduced sensitivity to adrenergic signals. This study shows that significant alterations at proximal and distal sites of the insulin secretory pathway in HC islets may support the hyperinsulinemic state of these rats.

Adaptation, Physiological↗

PubMed2000

Metabolic programming by nutrition during early development.

Incidence of obesity and diabetes is increasing at an alarming rate not only among the populations of the affluent nations but also amongst the populations of the developing nations. Understanding the mechanisms that cause the onset of these pathological conditions is a requisite to effectively tackling this problem. In this context the role of early nutritional experiences as a causative factor is being extensively investigated. This article briefly reviews the field of metabolic programming vis-a-vis an altered nutritional milieu during perinatal period and consequent adaptive metabolic patterning and metabolic imprinting in adult and/or consequent offspring.

Adaptation, Physiological↗

PubMed1999

A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats.

Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk formula results in the immediate onset of hyperinsulinemia. To evaluate these early changes, studies on pancreatic function were carried out on 12-day-old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectively, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islets secreted insulin in the absence of any added glucose and in the presence of Ca(2+) channel inhibitors. The activities of glucokinase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex were significantly increased in HC islets compared with MF islets. The protein contents of GLUT-2 and hexokinase were significantly increased in HC islets. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pancreatic function, causing the onset of hyperinsulinemia.

Age Factors↗