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

1995 ◽  
Vol 269 (4) ◽  
pp. E739-E744 ◽  
Author(s):  
S. G. Laychock ◽  
S. Vadlamudi ◽  
M. S. Patel
Keyword(s):  
Pancreatic Islet ◽  
First Generation ◽  
Cell Metabolism ◽  
Neonatal Rat ◽  
Male Rat ◽  
Female Rat ◽  
Adult Rats ◽  
Rat Pups ◽  
Glucose Sensitivity ◽  
Isocaloric Diets

Neonatal rat pups were artificially reared on isocaloric diets high in carbohydrate (HC) or high in fat (HF) or were naturally reared on mother's milk (MF). The HC adult rats were hyperinsulinemic, normoglycemic, and obese. This study investigates pancreatic islet insulin release (IR) of the adult first-generation (1-) diet-regulated animals and their second-generation (2-) progeny. Male rat 1-HC islets had higher basal IR than either 1-MF or 1-HF control groups. In addition, glucose (17 mM) failed to increase IR above basal values in 1-HC islets, whereas it stimulated IR in 1-MF and 1-HF islets. Similar secretory responses were evoked by 2-ketoisocaproic acid (2-KIC). Female rat 1-MF and 1-HF islets also had higher glucose-stimulated IR compared with 1-HC islets. Male rat 2-HC islets had higher basal IR and reduced sensitivity to glucose and 2-KIC compared with 2-MF islets, which coincided with hyperinsulinemia. Glyceraldehyde-3-phosphate dehydrogenase activity in 1-HC and 2-HC islets was higher than in MF islets. These data suggest that basal IR is higher in islets isolated from animals reared as neonates on a diet high in carbohydrate. Alterations in beta-cell metabolism and secretion probably contribute to the hyperinsulinemia, reduced glucose sensitivity, and glucose intolerance characteristic of this rat model.

Persistence of metabolic consequences in the progeny of rats fed a HC formula in their early postnatal life

1995 ◽  
Vol 269 (4) ◽  
pp. E731-E738 ◽  
Author(s):  
S. Vadlamudi ◽  
S. C. Kalhan ◽  
M. S. Patel
Keyword(s):  
First Generation ◽  
Adult Life ◽  
Female Rats ◽  
Postnatal Life ◽  
Female Rat ◽  
Tissue Mass ◽  
Male And Female ◽  
Rat Pups ◽  
Male And Female Rats ◽  
Early Postnatal Life

First-generation (1-) male and female rat pups were either reared artificially on a high-carbohydrate (HC) or a high-fat (HF) formula or nursed by mother (MF) from day 4 and weaned onto a stock diet on day 24. 1-HC rats compared with sex-matched control rats (1-HF and 1-MF) were hyperinsulinemic and mildly obese by day 60. We investigated the effect of maternal hyperinsulinemia on the second generation (2-) by intragroup breeding. The 2-HC male and female rats were hyperinsulinemic on day 45, had significantly increased growth rate from approximately day 60 onward, and became obese as evidenced by increased adipose tissue mass due to hypertrophy on day 100. The lipogenic capacity of liver and adipose tissues was significantly higher in the 2-HC than in control rats. Thus the metabolic changes that occurred in the first-generation rats fed a HC formula during early postnatal life not only persisted into their adult life but were also passed on to the next generation.

scholarly journals Repression of the Glucocorticoid Receptor Increases Hypoxic-Ischemic Brain Injury in the Male Neonatal Rat

2019 ◽  
Vol 20 (14) ◽  
pp. 3493 ◽  
Author(s):  
Katherine R. Knox-Concepcion ◽  
Johnny D. Figueroa ◽  
Richard E. Hartman ◽  
Yong Li ◽  
Lubo Zhang
Keyword(s):  
Brain Injury ◽  
Infarct Size ◽  
Glucocorticoid Receptors ◽  
Therapeutic Interventions ◽  
Neonatal Rat ◽  
Reflex Response ◽  
Female Rat ◽  
Neonatal Brain ◽  
Rat Pups ◽  
The Right

Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia is the most common cause of neonatal brain damage and results in significant neurological sequelae, including cerebral palsy. The current therapeutic interventions are extremely limited in improving neonatal outcomes. The present study tests the hypothesis that the suppression of endogenous glucocorticoid receptors (GRs) in the brain increases hypoxic-ischemic (HI) induced neonatal brain injury and worsens neurobehavioral outcomes through the promotion of increased inflammation. A mild HI treatment of P9 rat pups with ligation of the right common carotid artery followed by the treatment of 8% O2 for 60 min produced more significant brain injury with larger infarct size in female than male pups. Intracerebroventricular injection of GR siRNAs significantly reduced GR protein and mRNA abundance in the neonatal brain. Knockdown of endogenous brain GRs significantly increased brain infarct size after HI injury in male, but not female, rat pups. Moreover, GR repression resulted in a significant increase in inflammatory cytokines TNF-α and IL-10 at 6 h after HI injury in male pups. Male pups treated with GR siRNAs showed a significantly worsened reflex response and exhibited significant gait disturbances. The present study demonstrates that endogenous brain GRs play an important role in protecting the neonatal brain from HI induced injury in male pups, and suggests a potential role of glucocorticoids in sex differential treatment of HIE in the neonate.

PRODUCTION OF MALE PSEUDOHERMAPHRODITISM IN RATS BY TWO NEW INHIBITORS OF STEROID 17α-HYDROXYLASE AND C 17-20 LYASE

1976 ◽  
Vol 71 (3) ◽  
pp. 289-297 ◽  
Author(s):  
A. S. GOLDMAN ◽  
R. D. EAVEY ◽  
MARY K. BAKER
Keyword(s):  
Enzyme Inhibitors ◽  
Neonatal Rat ◽  
Male Rats ◽  
Male Rat ◽  
Pregnant Rats ◽  
Adult Rat ◽  
Rat Pups ◽  
Potent Inhibition

SUMMARY Two new synthetic steroid analogues, (I) 16β-bromo-3β,17α-dihydroxy-5α-pregnane-11,20-dione and (II) 17β-ureido-1,4-androstadien-3-one have been shown to give kinetic patterns consistent with active-site-directed irreversible inhibition of adult rat testicular microsomal steroid 17α-hydroxylase and C17-20 lyase in vitro. Administration of both analogues to adult male rats for 24 h produced potent inhibition of these testicular enzymes in vivo. Given to pregnant rats during the critical period of male organogenesis they produced hypospadias: a characteristic of the syndrome in man in which these enzymes are defective genetically. Given to male rat pups during the first 9 days of life, inhibitor II produced significantly smaller prostates and seminal vesicles in adulthood, indicating the usefulness of this inhibitor in studies on the role of testosterone in neonatal programming of target organ size in adulthood. Thus, two new enzyme inhibitors have been shown to block testosterone production in the foetal and neonatal rat selectively at the site of the hydroxylase without other apparent hormonal effects or influence on adrenal size.

QUANTITATIVE ANALYSIS OF PANCREATIC ISLET DEVELOPMENT AND INSULIN STORAGE IN THE FOETAL AND NEWBORN RAT

1975 ◽  
Vol 80 (4) ◽  
pp. 657-666 ◽  
Author(s):  
H. M. P. Freie ◽  
A. Pasma ◽  
P. R. Bouman
Keyword(s):  
Pancreatic Islet ◽  
High Rate ◽  
Neonatal Rat ◽  
Insulin Concentration ◽  
High Concentration ◽  
Differential Growth ◽  
Adult Rats ◽  
Islet Development ◽  
Islet Tissue ◽  
Insulin Storage

ABSTRACT Pancreatic islet development and insulin storage were studied in foetal rats during the last 4 days of gestation (day 19 to 22 post-coitum (p. c.)) and in 1 and 5 days old neonatal rats. Adult female virgin rats were also studied. The percentage of granulated B-cells per islet, the degree of B-cell granulation and the islet insulin concentration rose from low levels on day 19 to adult levels on day 22 and remained stable after birth. This indicates that the qualitative maturation of the pancreatic islets as insulin producing units is completed on the last day of gestation. The percentage of islet tissue slowly rose from 0.7 % at day 19 to 1.5 % on day 22. A further and much more rapid rise occurred during the first day of birth. At the 5th postnatal day the islets comprised 3.6 % of the pancreas versus 1.1% in adult rats. Likewise, the neonatal pancreatic insulin concentration was about 3 times higher than in the adult pancreas. The foetal pancreas as a whole showed rapid exponential growth between day 18 and 21 p. c., but a sudden decline in growth rate occurred from day 21 onward. The total mass of islet tissue, on the other hand, continued to expand at its high initial rate up to the first day after birth, whereafter this high rate also declined. The high concentration of insulin in the neonatal rat pancreas therefore appears to be due to differential growth rates of the endocrine and exocrine tissue during the last day of pregnancy and the first day after birth.

scholarly journals SAT-287 Mild Perinatal Undernutrition Results in Underweight Pups and a Premature Neonatal Leptin Surge

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tiffany K Miles ◽  
Melody Lyn Allensworth ◽  
Ana Rita Silva Moreira ◽  
Angela Katherine Odle ◽  
Anessa Haney ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Caloric Intake ◽  
Male Rat ◽  
Metabolic Dysfunction ◽  
Leptin Receptors ◽  
Gh Secretion ◽  
Maternal Undernutrition ◽  
Rat Pups ◽  
The Impact

Abstract Malnutrition causes dysregulated pituitary function, which may in part be due to lowered leptin signals. We showed that loss of somatotrope leptin receptors in mice reduces growth hormone (GH) secretion and promotes metabolic dysfunction in adults. More recently, we showed that adult male mice fasted for 12 or 24 hours also had significantly lowered GH secretion, which correlated with a 94% reduction in serum leptin. Malnutrition may result in changes in the leptin surge during neonatal development in rodents or the third trimester in humans. Severe (50% reduction) maternal undernutrition (1) blunted the surge in rodents, however less severe undernutrition (30% reduction) caused a premature leptin surge (2). Both studies reported that pups showed metabolic dysfunction as adults. In our studies of leptin regulation of somatotropes, we tested the more severe calorie restriction model and discovered significant pup and maternal loss. We then elected to develop a milder undernutrition model, which may relate more closely to society’s nutritional challenges with the objective of determining if the timing of the leptin surge had shifted. This maternal undernutrition study consisted of dams fed ad libitum (fed) and pair fed dams receiving 20% reduced caloric intake (undernourished). Undernutrition started at E15 and ended with sacrifice at various times during the leptin surge. While nursing, the undernourished dams did not lose weight, but their weight gain was reduced to 45% of that of fed dams. We have collected data from 177 neonatal pups and 19 fed or undernourished dams. At PND5 and PND10, pups from undernourished moms weighed significantly less (16.3% and 21.8%) than pups from fed dams. Additionally, weanlings (PND 21) from underfed dams exhibited a 28.04% reduction in weight and an 8.43% reduction in nose to anus length (p = 0.0005) compared to pups from control fed dams. The timing of the leptin surge in pups from fed dams was normal in female pups. However, pups from mildly undernourished dams had “premature” leptin surges that peaked 2 days earlier than normal. Ongoing studies are testing metabolic function in these mice, as adults, to determine their sensitivity to a 45% high fat diet and the impact on somatotrope functions. This model demonstrates that even a 20% reduction in nutrition will negatively impact offspring and shift the timing of the leptin surge. 1. Delahaye F, Breton C, Risold PY, Enache M, Dutriez-Casteloot I, Laborie C, Lesage J, Vieau D. Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. Endocrinology 2008; 149:470-475 2. Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y. Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell metabolism 2005; 1:371-378

scholarly journals Gender Differences Involved in the Pathophysiology of the Perinatal Hypoxic-Ischemic Damage

2019 ◽  
pp. S207-S217
Author(s):  
S. MURDEN ◽  
V. BORBÉLYOVÁ ◽  
Z. LAŠTŮVKA ◽  
J. MYSLIVEČEK ◽  
J. OTÁHAL ◽  
...  
Keyword(s):  
Gender Differences ◽  
Perinatal Asphyxia ◽  
Experimental Studies ◽  
Male Rat ◽  
Female Rat ◽  
Long Term Effects ◽  
Rat Pups ◽  
Hypoxia Ischemia ◽  
Long Term Consequences

Hypoxic-ischemic encephalopathy (HIE) is a neonatal condition that occurs as a consequence of perinatal asphyxia, which is caused by a number of factors, commonly via compression of the umbilical cord, placental abruption, severe meconium aspiration, congenital cardiac or pulmonary anomalies and birth trauma. Experimental studies have confirmed that male rat pups show a higher resistance to HIE treatment. Moreover, the long-term consequences of hypoxia in male are more severe in comparison to female rat pups. These sex differences can be attributed to the pathophysiology of hypoxia-ischemia, whereby studies are beginning to establish such gender-specific distinctions. The current and sole treatment for HIE is hypothermia, in which a reduction in temperature prevents long-term effects, such as cerebral palsy or seizures. However, in most cases hypothermia is not a sufficient treatment as indicated by a high mortality rate. In the present review, we discuss the gender differences within the pathophysiology of hypoxia-ischemia and delve into the role of gender in the incidence, progression and severity of the disease. Furthermore, this may result in the development of potential novel treatment approaches for targeting and preventing the long-term consequences of HIE.

Micturition reflexes in decerebrate and spinalized neonatal rats

1990 ◽  
Vol 258 (6) ◽  
pp. R1508-R1511 ◽  
Author(s):  
M. N. Kruse ◽  
W. C. De Groat
Keyword(s):  
Postnatal Development ◽  
Postnatal Period ◽  
Spinal Reflex ◽  
Neonatal Rat ◽  
Neonatal Rats ◽  
Adult Rats ◽  
Bladder Distension ◽  
Reflex Pathway ◽  
Rat Pups ◽  
Micturition Reflexes

Micturition in neonatal rats is mediated by a spinal reflex pathway activated by the mother licking the perineum (the perineal-to-bladder reflex, P-Bld). Micturition in adult rats is mediated by a spinobulbospinal reflex pathway activated by bladder distension (the bladder-to-bladder reflex, Bld-Bld). This study examines the postnatal development of the Bld-Bld reflex in decerebrate or spinalized unanesthetized and urethan-anesthetized rat pups 2-26 days of age. Urethan anesthesia depressed both the Bld-Bld and P-Bld micturition reflexes. Bld-Bld micturition reflexes (peak intravesical pressures of 13 +/- 6 cmH2O and durations of 35 +/- 11 s) were noted in 54% of 2-day-old decerebrate pups and in all of the 6- and 9-day-old decerebrate pups but in none of the 2- or 9-day-old spinalized pups. We conclude that a weak supraspinal Bld-Bld reflex is present during the early postnatal period; however, the P-Bld reflex is the primary mediator of micturition in the neonatal rat.

Sexual Behavior is Enhanced by Regular, Repeated Mating from Young Adulthood to Middle Age in Female Long-Evans Rats

2020 ◽  
Vol 13 (2) ◽  
pp. 169-177
Author(s):  
Fay A. Guarraci ◽  
Chantal M.F. Gonzalez ◽  
Devon Lucero ◽  
Lourdes K. Davis ◽  
Sarah H. Meerts
Keyword(s):  
Sexual Behavior ◽  
Mating Behavior ◽  
Preference Test ◽  
Sexual History ◽  
Female Rats ◽  
Male Rat ◽  
Female Rat ◽  
Repeated Mating ◽  
First Time ◽  
Mating Tests

Background: Aging is associated neuroendocrine changes in women. Animals can be used to model these changes, as well as changes in reproductive behavior. Objective: The current study was designed to characterize mating behavior across age and assess the effects of age and sexual history on mating behavior. Methods: Sexual motivation was assessed using the partner-preference test, in which a female rat is given the choice to interact with a same-sex conspecific or a sexually-vigorous male rat, with which she can mate. Results: Across repeated mating tests (2-12 months of age), female rats spent more time with the male, displayed more solicitation behaviors, were less likely to leave the male after mounts, but visited both stimulus animals less frequently. Comparing a separate group of age-matched, hormoneyoked female rats mated for the first time at 12 months of age to female rats mated for the first time at 2 months of age showed that the 12 month rats visited both stimulus animals less, were less likely to leave the male after mounts, took longer to return to the male after mounts, and displayed fewer solicitation behaviors than their younger counterparts. Relative to middle-aged female rats once they were sexually experienced, 12 month naïve rats spent less time with the male, were more likely to leave the male after mounts, and displayed fewer solicitation behaviors. Furthermore, 12 month naïve rats failed to discriminate between the stimulus animals, visiting both stimulus animals at the same rate unlike 2 month naïve or 12 month experienced rats. Conclusion: Taken together, these results suggest that aging affects some measures of sexual behavior, but most effects of age can be mitigated by regular, repeated mating.

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