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Apparent starvation-induced repression of pancreatic islet glucokinase.

Conflicting data were previously reported concerning the effect of starvation upon the glucokinase protein and glucokinase mRNA content of pancreatic islets. In the present study, conducted in fed rats and animals starved for 48 h, the catalytic activity of glucokinase in islet homogenates and the content of this enzyme in islets were both decreased by starvation to the same relative extent. These findings support the view that the altered metabolic and secretory response to D-glucose found in islets from starved rats may be attributable, in part at least, to an apparent repression of glucokinase.

Animals↗

The effects of G-CSF treatment and starvation on bacterial translocation in hemorrhagic shock.

BACKGROUND: Bacterial translocation is thought to be responsible for infectious complications after hemorrhagic shock. The aim of this study is to investigate the effects of granulocyte colony-stimulating factor (G-CSF) treatment on bacterial translocation in starved or fed animals subjected to hemorrhagic shock. MATERIALS AND METHODS: Fifty Wistar albino rats (200-275 g) were divided into six groups such as naive control (n = 7), G-CSF treatment (n = 7), hemorrhagic shock in starved rats (n = 9), hemorrhagic shock in fed rats (n = 9), G-CSF treatment 24 h before hemorrhagic shock in starved rats (n = 9), and G-CSF treatment 20 min after hemorrhagic shock in fed rats (n = 9). Hemorrhagic shock was induced by withdrawal of 2.1 ml/100 g blood via a carotid arterial cannulae placed under sodium pentobarbital anesthesia. Twenty-four hours later, mesenteric lymph nodes, liver, spleen, and peripheral blood samples were evaluated by using a quantitative microbiological technique and the numbers of colony-forming units were compared between groups. RESULTS: No bacteria was detected in samples from naive controls or G-CSF-treated unshocked rats. In animals subjected to hemorrhage, Escherichia coli was the predominant pathogen together with Streptococcus faecalis, Pseudomonas, and Lactobacillus species. In this model, starvation augmented the magnitude of bacterial translocation while G-CSF treatment has virtually abolished it. CONCLUSION: Under experimental conditions, preshock starvation increases gut-derived bacterial translocation and administration of G-CSF before or after hemorrhagic insult significantly reduces it.

Animals↗

Myocellular creatine and creatine transporter serine phosphorylation after starvation.

BACKGROUND: Myocellular creatine, which is critically important for normal energy metabolism, increases in rat gastrocnemius muscle after starvation via unknown mechanisms. Creatine (Cr) uptake across plasma membranes is governed by a single, specific transporter (CrTr) that shares 50% amino acid sequence identity with GABA/choline/betaine transporters whose functions are modulated by phosphorylation. METHODS: Gastrocnemius muscle was collected from adult male Sprague-Dawley (225-250 g) rats that were randomized to receive normal rat chow and distilled water ad libitum (CTL) or distilled water alone for 4 days (STV). Total Cr, phosphocreatine (PCr), free Cr, and ATP were measured luminometrically. CrTr protein expression and protein serine and tyrosine phosphorylation and mRNA expression were determined using immunoprecipitation and quantitative Western blotting and reverse transcription polymerase chain reaction (RT-PCR) analyses, respectively. Guanidinoacetate methyltransferase (GAMT) activity, guanidinoacetic acid (GAA) content, creatine kinase (CK) activity, and creatinine (Crn) content were assayed luminometrically or spectrophotometrically. Creatine transporter uptake activity was also measured in skeletal muscle membrane vesicles. Data were analyzed by t test. RESULTS: Total Cr and free Cr increased 26 and 280% in STV (32.3 +/- 1.0 and 12.9 +/- 1.4 vs 25.7 +/- 1.1 and 3.4 +/- 0.9 micromol/g wet wt, mean +/- SEM, respectively, P < 0.01) whereas PCr content decreased 18% (18.6 +/- 0.8 vs 22.8 +/- 0.9 micromol/g wet wt, STV vs CTL P < 0.05). CrTr protein and mRNA expression, ATP, GAA, CK, GAMT, and protein tyrosine phosphorylation of CrTr were not significantly different between the two groups. However, protein serine phosphorylation of CrTr was significantly reduced by 30% (P < 0.05) and creatine uptake activity was significantly increased (P < 0.05) in starved animals. CONCLUSION: Increases in myocellular creatine content after starvation are associated with reduced serine phosphorylation of the creatine transporter.

Animals↗

Dose-dependent pancreatotrophic effect of cholecystokinin-octapeptide in the rat: the influence of starvation.

Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the exocrine pancreas, whereas at high doses, they produce pancreatic injury. This study was carried out to study the effect of starvation on the dose-dependent pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 micrograms kg-1, respectively, twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and trypsin inhibitor (PSTI) contents as well as histology were examined. In normal rats, CCK-8 increased the pancreatic content of protein, amylase, serine proteases and PSTI with maximum values between doses of 2 and 16 micrograms kg-1. The dose of 32 micrograms kg-1, however, yielded less trophic responses. Given to fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme contents of the pancreas with maximum values between doses of 1 and 4 micrograms kg-1. The first dose supramaximum for the trophic responses was as low as 8 micrograms kg-1. Histology revealed necroinflammatory damage (acinar cell vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum doses of CCK-8 in both groups. Cell necroses and vacuolization were less but present even at doses optimum for trophism and exhibited dependence on both the dose of CCK-8 and nutrition. In either the normal or fasted animals, the periinsular acini were relatively less affected by the toxic effects of CCK-8 than the teleinsular ones. The results indicate that starvation makes the exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The relative protection seen in periinsular acini suggests a modulatory influence of islet hormones on development of CCK-induced acinar cell injury.

Animals↗

Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization.

The zonal distribution of phosphoenolpyruvate carboxykinase (PCK) and tyrosine aminotransferase (TAT) mRNA in liver was studied by in situ hybridization with radiolabelled cRNA probes and the abundance of PCK and TAT mRNA was quantified by Northern blot analysis of total RNA with biotinylated cRNA probes. Livers were taken from rats during a normal 12 h day/night rhythm, when they had access to food only during the dark period from 7 pm to 7 am, or during refeeding, when they had access to food after having been starved for 60 h. 1. Daily feeding rhythm: High levels of PCK mRNA were distributed mainly in the periportal and intermediate zone during the fasting period at noon and 6 pm. Feeding caused a rapid decrease in PCK mRNA level and a restriction of PCK mRNA localization to the periportal area within the first 2 h. No further alterations were observed during the following hours of the feeding period. TAT mRNA was distributed also in the periportal and intermediate zone during the fasting period. Feeding first reduced the mRNA level without changing the distribution pattern. Then towards the end of the feeding period TAT mRNA increased again to half-maximal levels and became restricted mainly to the periportal area. 2. Starvation-refeeding cycle: High amounts of PCK mRNA as well as of TAT mRNA were localized predominantly in the periportal and intermediate zone after 60 h of starvation. PCK and TAT mRNA both decreased markedly during the first 2 h of refeeding and then remained almost constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ultrastructure of the absorptive cells in the small intestine of the rat during starvation.

The ultrastructure of the absorptive cells in the duodenum, jejunum and ileum after 7, 14 and 21 days of starvation was investigated using rats aged from 12 to 18 months weighing about 500 g. In the basal cytoplasm of the absorptive cells (in the duodenum and ileum of 21-day-starved rats and the jejunum of 14- and 21-day-starved rats), the following changes were found: atrophied mitochondrion-like bodies, small vesicles, a short and sparse rough-surfaced endoplasmic reticulum and a lack of density in a portion of the cytoplasm. Moreover, many autolysosomes of various sizes and shapes were encountered in the basal cytoplasm; occasionally these elements accumulated and appeared to fuse to one another. In contrast, in the apical cytoplasm of absorptive cells in the intestine of starved rats, the ultrastructure was similar to that of control rats. It was considered that the apical cytoplasm of the absorptive cells in the starved rat intestine might be preserved as long as possible during starvation in order to absorb nutrients when they become available again.

Animals↗

Sex-specific regionality of liver metabolism during starvation; with special reference to the heterogeneity of the lobular periphery.

Staining procedures for glucose-6-phosphatase and 3-hydroxybutyrate dehydrogenase activity and for glycogen were used to investigate adaptive changes in the regionality of hepatic gluconeogenesis and ketogenesis in fasting male and female rats. A reciprocal distribution of gluconeogenic and ketogenic capacities was found in both sexes, but male and female animals were different with respect to: a) the time necessary for full induction of glucose-6-phosphatase activity (24 h in females, 48 h in males); b) the overall activity of 3-hydroxybutyrate dehydrogenase; and c) glycogen content. The activity of the latter enzyme and the glycogen content did increase with time of starvation, but at all times, were higher in males, than in females. Results, thus, indicate that the extent to which ketone bodies replace glucose as major fuel for the brain is larger in males than in females. This may explain the delayed induction of glucose-6-phosphatase activity and the higher glycogen content in the male during starvation. Distributions of enzyme activities and of glycogen, furthermore, revealed the heterogeneity of the lobular periphery, i.e. functional differences among sinusoids dependent upon whether they originate from the portal tract or the vascular septum, and thus confirm the lobular concept proposed by Matsumoto et al. (1979).

Animals↗

Effects of starvation and refeeding a high carbohydrate diet on the intra-acinar distribution pattern of phosphoenolpyruvate carboxykinase activity in the liver of male and female rats.

Phosphoenolpyruvate carboxykinase activity in rat liver was shown to be heterotopically distributed within the acinus under varying feeding conditions. Highest values of PEPCK activity were found in the periportal zone of the acinus from where it decreased continuously towards the perivenous zone. 84 h of starvation resulted in an increase of activity, which was most prominent in the perivenous zone, but nevertheless resulted in a steeper gradient. Refeeding of starved rats with a high carbohydrate diet for 6 nights led to a decrease in PEPCK activity which was most prominent in the periportal zone, but almost negligible in the perivenous zone, resulting in a further change in the activity gradient. Sex-dependent differences for total PEPCK activity were found i) in controls, where the activity was lower in females, ii) after starvation, where the induction was much higher in females, and iii) after refeeding of starved rats, where the activity in females remained higher compared to that of the controls. Differences in the intra-acinar localization of the activity in dependence of the sex were registrated in the control group and in starved rats. Livers from female rats contained a higher periportal/perivenous ratio compared to males. In starved and starved and refed animals the periportal/perivenous ratios were almost the same in both sexes.

Animals↗

Effect of starvation or streptozotocin-diabetes on phosphate-activated glutaminase of different rat brain regions.

Phosphate-activated glutaminase (PAG) was assayed in homogenates of brain cerebellum, hippocampus or striatum from normal, starved for 48 h to 120 h or streptozotocin-diabetic rats. Only the hippocampal enzyme was increased (47%) by diabetes. Starvation had no effect in any of the regions studied. PAG of synaptosomes or of non-synaptosomal mitochondria from the hippocampus was also increased by 48% and 22% respectively in diabetes. PAG of synaptosomes from the cortex, the cerebellum, or the striatum or of the non-synaptosomal mitochondria from the cortex were not affected by diabetes or prolonged (120 h) starvation. A suggestion is presented that peripheral insulin, indirectly, may regulate PAG activity in a specific region of the rat brain.

Animals↗

Retardation of fetal brain cell growth during maternal starvation: circulating factors versus altered cellular response.

Maternal starvation inhibits fetal brain development during late gestation in the rat. To determine whether intrinsic or extrinsic factors might be the principal contributor to altered growth, brain cells from 20 day fetuses were cultured in a 96 well plate with MEM and 10% adult rat serum. Tissue growth was monitored by spectrophotometric measurement of the mitochondrial reduction of a chromagen 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT). After 1, 4 or 6 days incubation, MTT activity in non confluent cultures was shown to be directly related to tissue mass. When fetal brain cell cultures were incubated with 1% and 10% concentrations of adult rat serum, an 11-fold increase in MTT activity paralleled a 15-fold increase in tritiated thymidine incorporation. The impact of maternal starvation on fetal brain cell growth was examined by measuring MTT activity in fetal brain cells from fed and starved mothers. When cultures were incubated for 6 days with graded concentrations of fed adult serum (1.25-10%), the MTT response was slightly but consistently lower in cells from starved when compared with cells from fed mothers. By contrast, a marked difference in MTT activity which was paralleled by a lower DNA content became apparent when fetal rat brain cells were incubated with starved adult serum. Fetal serum and adult male serum were found to support growth equally well, while incubation of fetal brain cells with maternal sera resulted in lower MTT values than with the corresponding fetal sera. When cells were incubated with fetal sera pooled from starved mothers, MTT activity was decreased by 42 to 45%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regional brain glucose use in unstressed rats after two days of starvation.

Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6-14C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation.

Animals↗

Activity alterations of metabolic enzymes in the anterior pituitary of female rats during acute and chronic starvation, as well as after refeeding.

The activity of glycolysis and hexose monophosphate shunt decreases while the activity of some oxydative enzymes and acid phosphatase increases in the anterior pituitary of adult female rats during starvation. The alterations depend on the severity of starvation. The polypeptide hormone production also decreases. A close relationship exists between the metabolic activity of the gland and its endocrine function.

Acid Phosphatase↗

Differential utilization of long chain fatty acids during triacylglycerol depletion. II. Rat liver after starvation.

Rats starved for 96 hr were shown to have a 94% reduction in liver triacylglycerol. Among the long chain fatty acids in liver triacylglycerol, only stearic acid and arachidonic acid were proportionally increased (2.5 and 6 times, respectively); palmitic and linoleic acids were unchanged, and palmitoleic and oleic acids were proportionally decreased. Stearic and arachidonic acids (mg%) were correlated positively within the triacylglycerol fraction, and both fatty acids varied inversely with total triacylglycerol (mg/g) in fed and starved rats. The utilization of long chain fatty acids from liver triacylglycerol during starvation resulted in selective retention of arachidonic acid and stearic acid and suggests that differential hydrolysis of liver triacylglycerol by hepatic lipase may occur or selective reacylation of these specific fatty acids may occur during starvation.

Animals↗

A morphometric study of the inhibition of autophagic degradation during restorative growth of liver cells in rats re-fed after starvation.

In the parenchymal cells of the liver of adult male rats re-fed on the evening of the fifth day after a period of absolute starvation, a nearly complete absence of autophagic vacuoles (AV) has been found by the morphometric determination of the fractional cytoplasmic volume of AV. The mean value for that parameter increased only gradually during periods of re-feeding. The value was found to be in the range of the control values only on, or after, the fifth day of re-feeding. As in previous experiments, in the control animals the number of AV was again found to be dependent on a circadian rhythm with maxima during the light, and minima during the dark, periods. This rhythm reappeared in the period of re-feeding without a shift in phase. In the controls as well as in the re-fed animals the "segregated fraction" was highest for microbodies, intermediate for mitochondria and glycogen, but rather low for the remaining components of the cytoplasm. It is suggested that the long term inhibition of cellular autophagy, found in the present study, plays an important role in the restorative cellular growth of the liver during the recovery from the atrophy induced by starvation.

Animals↗

The effects of starvation and refeeding on intestinal cell proliferation in the mouse.

The effects of starvation and refeeding on intestinal cell proliferation were studied in four sites of the mouse intestine. Control mice were studied at different times of day in order to compensate for any circadian variations in proliferation. A circadian rhythm in crypt cell production rate was observed in all the sites of the small intestine and colon, and this rhythm appeared to be entrained to the food intake. The fractional crypt cell production rate decreased in all sites of the intestine after 24 h starvation, and remained low until 9 h after refeeding, when there was a marked increase in the crypt cell production rate of all the small intestinal sites, especially the proximal sites. There was little change in colonic crypt cell production rate until 12 h after refeeding, when there was a large increase in cell production. The crypt cell production rate of all sites then returned to control values for the remainder of the investigation. Crypt cell number decreased after refeeding and villus cell number increased, however a similar effect was observed in the control animals, nevertheless the changes in villus cell population of the refed mice occurred before any increase in crypt cell production, suggesting that cell migration from crypt to villi is not immediately dependent on cell proliferation.

Animals↗

Starvation injury after gastric reduction for obesity.

Gastric reduction operations are designed to control body weight by establishing a small, meal-size juxtaesophageal, gastric pouch that empties into the jejunum (gastric bypass) or the larger portion of the stomach (gastroplasty). If the outlet of the pouch is too small, a patient may be limited to ingesting clear liquids. Vomiting then occurs if heavier liquids or normal foods are taken. An occasional patient has difficulty eating properly and vomits even though the pouch volume and outlet are of optimum size. For a patient who reports vomiting, a distinction must be made between episodic improper eating and uncontrolled starvation. Three types of starvation injury are described: (1) sudden death from protein malnutrition; (2) refeeding syndrome; and (3) Wernicke-Korsakoff syndrome. The mechanisms of the development, manifestations, prevention, and treatment of these complications are explained. Surgeons who treat severe obesity should be aware of these complications and be prepared to manage patients who have uncontrolled vomiting so that such complications either do not develop or are recognized and treated as early as possible before serious and irreversible injury occurs.

Female↗

Changes in glucose, glycogen, thyroid activity and hypothalamic catecholamines in tench by starvation and refeeding.

The effects of short-term food deprivation (7 days) and refeeding (2 days) on different biochemical and neuroendocrine parameters were studied in tench. A 7-days fast resulted in a significant reduction of plasma glucose and glycogen hepatic content, supporting the key role of liver glycogen as energy depot for being consumed during fasting. The rapid recovery of normal values of blood glucose and glycogen stores by refeeding indicates a rapid replenishment of liver glycogen stores. The short-term starvation decreased circulating thyroid hormones (both T3 and T4) and T4 release from thyroid, supporting an interaction between nutritional state and thyroid function in tench. All these metabolic and hormonal changes were partial or totally reversed under refeeding conditions. An increase in hypothalamic content of norepinephrine and dopamine was found in fasted fish. This result might be a consequence of stress induced by starvation.

Analysis of Variance↗