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C J Cha

Publications and source records attributed to C J Cha.

At least 19 recordsLinked to original sources
PubMed1991

The cross-generation effect of neonatal macrosomia in rat pups of streptozotocin-induced diabetes.

To study the cross-generation effect of enhanced growth in macrosomic newborn rats, we induced mild hyperglycemia in 15 pregnant Sprague Dawley rats by intraperitoneal injection of streptozotocin, 35 mg/kg body weight, on the 5th d of gestation. As reported previously, we produced hyperinsulinemia and accelerated growth in the fetuses of hyperglycemic dams. We also showed that the macrosomic female pups (second generation) continued to have a higher growth rate through the first 12 wk of life. In this study, the second-generation female rats were mated with macrosomic second-generation males; they demonstrated glucose intolerance during late pregnancy and delivered pups (third generation) with higher birth weight and plasma insulin levels than the pups from control second-generation rats. When the macrosomic third-generation pups were raised under identical nutritional and environmental conditions as controls, the macrosomic rats showed accelerated growth and higher fat tissue weight during the first 12 wk of life. Furthermore, the macrosomia was associated with glucose intolerance and higher insulin to glucose ratios compared to controls. We also mated the offspring of second-generation streptozotocin-injected nonmacrosomic as well as the offspring of macrosomic pups of buffer-injected dams; none of the pups from these matings were significantly macrosomic. Therefore, we conclude that the perpetuation of obesity and possibly glucose intolerance across generations in this rat model is predominantly a result of abnormal intrauterine metabolic environment rather than genetic factor driven.

Animals↗
PubMed1991

Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique.

Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance in vivo, hyperinsulinemic-euglycemic clamp studies were performed. Ten-wk-old rats were fasted overnight, and porcine insulin was infused (2.4 mU.kg-1.min-1). Glucose was infused concurrently at varying rates to maintain euglycemia for 40-60 min. Insulin levels were raised from a baseline value of 163 +/- 57 pmol/L (23 +/- 8 microU/mL) (SD) to 476 +/- 57 pmol/L (67 +/- 8 microU/mL) at steady state for males and from 178 +/- 43 pmol/L (25 +/- 6 microU/mL) to 454 +/- 43 pmol/L (64 +/- 6 microU/mL) for females. The results showed that the macrosomic male and female animals were significantly less sensitive to the effects of insulin than were their respective controls; this was evident by a lower increment in glucose disposal rate per unit increase in insulin (0.04 +/- 0.01 versus 0.11 +/- 0.03 for males and 0.05 +/- 0.03 versus 0.18 +/- 0.07 mg.kg-1 per microU/mL for females). The endogenous glucose production by the liver in the basal (fasted) state in the macrosomic group compared to controls was higher, suggesting possible hepatic insulin resistance. However, endogenous glucose production was suppressed to the same degree between the experimental and control groups during the hyperinsulinemic period, suggesting that the hepatic insulin resistance can be overcome by high insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Glucose metabolism in adipocytes of obese offspring of mild hyperglycemic rats.

Six pregnant rats were made mildly hyperglycemic by intraperitoneal injection of streptozotocin on d 5 of gestation. Four control rats were injected with citrate buffer. Thirty pups born to experimental dams who had increased birth weight (birth weight greater than 1.7 SD of mean birth weight of pups from control dams) maintained accelerated growth through 10 wk of age. At 10 wk, oral glucose tolerance tests showed higher glucose and insulin levels than the controls (n = 37). In addition to the higher body weight, the experimental rats also had higher fat weight to body weight ratios. Adipocytes of epididymal fat from obese males and periovarian fat from obese females had higher lipid content with significantly larger cell size than the adipocytes of the controls. The adipocytes of macrosomic rats showed attenuated response to insulin-stimulated glucose conversion to total lipid and fatty acid when compared with the responses seen in the adipocytes of the control rats. Interestingly, although the insulin-stimulated glucose conversion to CO2 was similar in macrosomic and control males, the response in the macrosomic female was blunted when compared with that of the control females. Insulin receptor binding capacities of the macrosomic rats were lower than those of the controls, which is consistent with a phenomenon of down-regulation. However, the receptor affinities were higher in the experimental animals than in controls. Therefore, a postreceptor defect may account for the abnormality in glucose metabolism in the obese rats. In conclusion, the abnormal response to oral glucose loading in these experimental obese, hyperinsulinemic rats is due to peripheral tissue insulin resistance that is probably postreceptor in nature.

Adipose Tissue↗
PubMed1989

Neonatal sympathoadrenal response to acute hypoxia: impairment after experimental intrauterine growth retardation.

Sympathoadrenal system function may be altered following intrauterine growth retardation (IUGR). We tested the hypothesis that the growth-retarded newborn rat pup has increased basal sympathoadrenal activity under normoxic conditions and a blunted sympathoadrenal response to acute hypoxia. IUGR was established by uterine artery ligation on d 18 of gestation in Sprague-Dawley rats. Growth-retarded pups were chosen as those whose birth wt was more than 2 x SD below the mean birth wt of control pups delivered to sham-operated dams. At 24 +/- 12 h of age cardiac sympathetic neuronal activity (CSNA) was determined by 3H-norepinephrine tracer and alpha-methyltyrosine techniques. Adrenal medullary catecholamine synthesis (CAT SYN) was measured by 14C-tyrosine precursor methods, and adrenal catecholamine release (CAT REL) was determined using alpha-methyl-tyrosine. IUGR and control pups were studied over a 120-min period of normoxia or hypoxia (FiO2 = 0.09). Under normoxic conditions, the IUGR pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to controls. Adrenal CAT REL in normoxic IUGR pups was selective for epinephrine. In response to acute hypoxia, control pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to normoxic controls, with the proportion of norepinephrine and epinephrine released mimicking the ratio of the two amines in the adrenal. In contrast, in hypoxic IUGR pups CSNA and adrenal CAT SYN did not increase, and norepinephrine alone was released from the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1988

Maternal hyperglycemia in pregnant rats: its effect on growth and carbohydrate metabolism in the offspring.

Mild hyperglycemia during the last half of pregnancy was achieved by administration of streptozotocin to pregnant rats on the fifth day of gestation. Citrate buffer (vehicle for streptozotocin) was administered to control rats also on the fifth day of gestation. The pups born to the streptozotocin-treated mothers had higher birth weight, pancreatic insulin content, plasma insulin, and C-peptide concentrations compared with pups born to control mothers. The plasma glucose concentrations of the pups were similar between the two groups. The pups who were identified as macrosomic (birth weight greater than 1.7 SD than the mean of the control pups) maintained an accelerated postnatal growth through the first 10 weeks of age in female rats and in the first 3, and at 5 and 6 weeks of age for the male rats. The accelerated growth in the female rats was associated with higher perirenal-ovarian and salpingeal fat weight at 6 weeks. At 10 weeks of age, higher plasma insulin and glucose concentrations were observed following oral glucose challenge in both male and female macrosomic rats than in the control rats. At 12 weeks of age, only the female macrosomic rats showed abnormal glucose response due to peripheral insulin resistance. In the male rats at 12 weeks of age, a higher plasma insulin concentration in the macrosomic group was associated with a normal plasma glucose response to oral glucose challenge. We conclude that mild maternal hyperglycemia in rats resulted in fetal hyperinsulinemia and accelerated fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Growth and cellular composition in rats with intrauterine growth retardation: effects of postnatal nutrition.

We evaluated the catch-up growth of rats with intrauterine growth retardation (IUGR) raised in normal litters (8-10 pups) or in large litters (14-16 pups) during the first 2 wk of life. We also studied the influence of nutrition on cellular composition at birth and at 2 wk. Fifty-four pups (27 IUGR and 27 controls) were enrolled into normal or undernutrition groups. Postnatal undernutrition resulted in significantly lower growth in both control and IUGR rat pups than in normally fed pups. In the control group, postnatal undernutrition resulted in a lower liver weight but not a lower brain weight. Underfeeding of the IUGR group produced a greater number of cells of the brain and liver, but with smaller cell size than in normally fed IUGR rats. We conclude that compensatory catch-up growth in the mild-IUGR rat occurs if the postnatal nutrition is adequate. When postnatal nutrition is restricted, the non-IUGR rats became malnourished at 2 wk of age and the mild-IUGR rats did not demonstrate the catch-up growth phenomenon as was seen in those with adequate nutrition. In the severe-IUGR rat, undernutrition further compromised growth rate, so that at 2 wk of age their weights were the lowest of all the groups studied.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Accelerated growth and abnormal glucose tolerance in young female rats exposed to fetal hyperinsulinemia.

This study was designed to evaluate the relationship between fetal macrosomia and postnatal growth as well as the glucose homeostasis in young female rats. We produced fetal macrosomia by fetal insulin injection at 20 1/2 days of gestation. The control subjects were injected with saline. The weights were recorded weekly from birth up to 12 wk. Only the female rats were studied. At 4, 6, 10, and 12 wk of age, oral glucose tolerance tests were performed. Also, at wk 6, 10, and 12, peri-renal-ovarian-salpingeal fat weights, the RNA, DNA, and protein contents of the abdominal muscle were determined. One-hundred seventeen control and 78 macrosomic rats were studied. The macrosomic rats showed a higher body weight (10-12%) than the control rats from birth up to 8 wk, but at 10 and 12 wk their weights were similar. The fat weights reflected the body weights, i.e. a higher fat weight in the macrosomic rats during the period of accelerated growth (from birth up to 8 wk), and a similar fat weight when the body weight of the two groups were similar at 10 and 12 wk. At 4 and 6 wk of age, the plasma glucose level measured in response to the oral glucose loading were similar in both groups. However, at 10 and 12 wk of age, the macrosomic rats had significantly higher fasting plasma glucose levels and exhibited consistently higher plasma glucose levels for the 3.5-h period of postglucose administration compared to the control rats. The plasma insulin levels rose significantly following glucose challenge. However, the values were similar in both groups at 10 and 12 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of respiratory acidosis on glucose homeostasis in experimental intrauterine growth retardation in rats.

Hypoglycemia and asphyxia account for a significant proportion of morbidity in the infant with intrauterine growth retardation (IUGR). The purpose of this study was to evaluate changes in glucose homeostasis in IUGR rats during acute respiratory acidosis. IUGR was produced by bilateral uterine artery ligation at 17 days of gestation in 14 pregnant rats with 23 successfully delivered pups. The normal pups (n = 31) were those whose mothers were sham operated at the same gestational period. The IUGR and normal pups were studied at 2 days of age. One group of pups was studied under room air while another was subjected to 20 min of exposure to a gas mixture of 10% O2/15% CO2, balanced with N2. Gluconeogenesis in the liver and carcass, as well as plasma glucose and catecholamines were determined before and after the exposure to the gas mixture. The results showed that the 2-day-old IUGR rats have lower body weight (P less than 0.001), liver weight (P less than 0.001), plasma glucose (P less than 0.001), and rate of gluconeogenesis (P less than 0.01) when compared with the normally grown rats. During respiratory acidosis, the normally grown rats showed an increase in plasma epinephrine (P less than 0.005) without significant change in plasma glucose and rate of gluconeogenesis. The IUGR rats on the other hand, demonstrated a decrease in rate of gluconeogenesis (P less than 0.02), an increase in plasma glucose (P less than 0.001) while the plasma epinephrine level remained unchanged. We speculate that respiratory acidosis blunted cellular metabolism in the IUGR rat resulting in decreased peripheral glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1986

Growth and fatty acid metabolism in experimental intrauterine growth retardation: effect of postnatal nutrition in rat.

Rats, 3 1/2 to 4 d of age, were used to study weight gain and fatty acid (FA) metabolism as a function of degree of intrauterine growth retardation (IUGR) and of postnatal nutrition. The IUGR, quantified postnatally as mild and severe, was produced by uterine artery ligation on d 17 of gestation, and controls were shamoperated. Food intake was manipulated by varying the litter size; i.e., pup number per dam was 4 or 5 for overfeeding, 8-10 for normal feeding and 13-15 for underfeeding. Fatty acid synthesis rate (FASR) (determined by tritiated water incorporation in FA) and contents were determined in selected organs at 84 to 96 h of age. The initial weights (grams) at 2 to 12 h of age were: 5.88 +/- 0.74 (mean +/- SD) for controls, 5.18 +/- 0.11 for mild IUGR and 4.18 +/- 0.24 for severe IUGR. During the first 96 h of life, weight gain was less in underfed control pups while overfeeding resulted in the same weight gain as in normally fed pups. Pups with mild IUGR showed the same effect of under- or overfeeding as control pups. In the severe IUGR groups, weight gains were similar in all three feeding groups. In the carcass, the fatty acid content was reduced as a result of both prenatal and postnatal undernutrition. Although the underfed control group had a high FASR, underfeeding had no effect on the FASR of groups with IUGR. In the liver, the FA content was also lower in the underfed controls and in IUGR groups, without any difference in FASR. Feeding did not influence the FASR of liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Relationships among maternal and fetal amino acid blood concentrations and amniotic fluid amino acid levels in pregnant rhesus monkeys.

This study was designed to explore relationships among maternal and fetal amino acid blood concentrations and amniotic fluid amino acid levels in pregnant rhesus monkeys. Although there was no constant pattern for all amino acids in the three body fluids, we observed specific patterns for most neutral amino acids, imino acids, and acidic amino acids relative to their concentrations in maternal blood, fetal blood, and amniotic fluid. Moreover, there was no correlation between fetal phenylalanine blood levels and phenylalanine concentrations in amniotic fluid indicating that amniotic fluid phenylalanine levels would not be useful to monitor fetal phenylalanine blood concentrations during pregnancy.

Amino Acids↗
PubMed1985

Cell solute composition and potassium effects in slices of the rectal gland of the dogfish shark (Squalus acanthias).

Cell solute composition and apparent intracellular ionic concentrations (subscript i) were determined in rectal gland slices of the dogfish shark (Squalus acanthias). On aerobic incubation in elasmobranch Ringer's at 15 degrees C, the steady state values were: Ki+, 151 mM, close to its apparent electrochemical equilibrium; Cai2+, 1.7 mM; Mgi2+, 7.5 mM; Cl1-, 97 mM (maintained against its electrochemical potential gradient); the sum (Nai+ + Ki+) was about 66 meq/kg cell water lower than in the medium. Of free amino acids, only the effectively impermeable anionic taurine (32 mM) and glutamate (3.7 mM) significantly contribute to the Donnan system. Variations of the Ringer's K+ concentrations, or the presence of 0.5 mM ouabain, demonstrated the permeability of the cell membrane to na+, K+, and Cl-. Cell volume changes: 0.5 mM ouabain produced a gradual swelling and ionic changes consistent with an inhibition of the sodium pump. In high-K+ media the cells swelled massively and the membrane depolarized. A linear relationship between cell volume changes and the Nernst potential for K+ was found. These properties are consistent with a pump-and-leak system for cell volume maintenance. The K+ -induced cell swelling was found to be reversible on transfer of the tissue to regular Ringer's. The extrusion of cell water was associated with an influx of Na+ into, and an efflux of K+ from, the cells (both fluxes down-hill), as well as extrusion of Cl- against its concentration gradient.2+

Amino Acids↗
PubMed1985

Postnatal growth and fatty acid synthesis in overgrown rat pups induced by fetal hyperinsulinemia.

Fetal hyperinsulinemia in the rat results in increased body weight, lipid content, and enhanced lipogenesis in liver and carcass. The purpose of our study was to determine whether the macrosomia and enhancement of fatty acid (FA) synthesis and/or content persisted postnatally in this animal model. Fetal hyperinsulinemia was produced in Sprague-Dawley rats by injecting fetuses with 2 units of insulin at 20.5 days of gestation. Alternate pups in the same litter were injected with saline. Pups were delivered surgically at 22.5 days of gestation, were weighed daily and sacrificed on day 15. FA content and synthesis rates of liver and skeletal muscle were measured. We found: (1) At birth, insulin-treated pups were 12% heavier than saline littermates, (5.88 +/- 0.14 g v 5.26 +/- 0.14 g, P less than .01); and (2) The enhanced growth associated with prenatal insulin treatment persisted during the suckling period, ie, compared with saline-treated controls, insulin pups were 15.7% heavier at 15 days of age (P less than .01); growth velocity of insulin pups, beginning on day 3, significantly exceeded that of control pups (P less than .05). FA contents of liver and muscle in insulin pups, (62.6 +/- 5.7 mumol/g and 62.7 +/- 13.2 mumol/g) were significantly greater (P less than .05) than in saline littermates (45.1 +/- 5.6 mumol/g and 30.2 +/- 4.7 mumol/g, respectively). We conclude that.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Muscle glutamine production in diabetic ketoacidotic rats.

The mechanism of activation of glutamine production by the hindlimb during diabetic ketoacidosis (DKA) was investigated in rats. Muscle glutamine production was estimated to account for over 90% of the total glutamine produced by the hindlimb. DKA produced significant increases in the concentrations of NH4+ and IMP in hindlimb muscles, suggesting that AMP deaminase is activated by DKA. NH4Cl- and HCl-induced acidosis did not produce these changes, indicating either that acidosis itself is not the stimulus for increased AMP deaminase activity or that the more severe degree of acidosis accompanying DKA is necessary for activation. Muscle glutamine concentrations were depressed in DKA. Experiments with isolated epitrochlearis muscle showed that the transport and permeability properties of the muscle cells (as judged by uptake and release of alpha-aminoisobutyrate and glutamine) were not altered by DKA. However, glutamine uptake by muscle cells was significantly inhibited by L-leucine, the concentration of which, along with other branched-chain amino acids, is markedly elevated in DKA.

Adipose Tissue↗
PubMed1983

Placental transfer of aromatic amino acids in non-human primates.

Macaca fascicularis (crab-eating monkeys) underwent an operative procedure at 120 to 130 days of pregnancy that allowed fetal blood sampling. During subsequent experiments L-phenylalanine and p-chlorophenylalanine were injected into the maternal circulation. Blood obtained from mother and fetus revealed that phenylalanine is actively transported across the placenta and hence is markedly increased in the fetus if the maternal blood phenylalanine concentration is below the "saturation" level of 1.82 mM to 2.12 mM. The results of these studies which provide a better understanding of placental transport mechanisms of aromatic amino acids will be of assistance in future management of pregnant phenylketonuric females.

Amino Acids↗
PubMed1981

Therapeutic attempts in infants with nonketotic hyperglycinaemia.

Identical male twins with non-ketotic hyperglycinaemia did not exhibit any development progress while on strychnine treatment. Since other therapeutic attempts with single agents previously had failed in most instances, we tried a combination of various treatment modalities. The results indicated that the administration of glycine receptor antagonist (strychnine) together with a low-protein diet (1.5 gm/kg/day), augmentation of 1-C units (N(5)-formlytetrahydrofolate), and removal of glycine from extracellular fluid (sodium salicylate and sodium benzoate) yielded some clinical improvement and positive biochemical changes in out patients.

Adrenocorticotropic Hormone↗