PubMed Health⌕ Search

Biomedical subjects

K Snell

Publications and source records attributed to K Snell.

At least 73 records · Page 4Linked to original sources

Glucose metabolism in the newborn rat: the role of insulin.

The effect of the administration of anti-insulin serum to newborn rats, surgically delivered under ether anaesthesia at term, was examined with respect to liver glycogen concentration and plasma concentrations of glucose, lactate and free fatty acids. Newborn rats thus treated showed decreased liver glycogen concentrations and elevated plasma concentrations of glucose, lactate and free fatty acids compared to untreated control animals one hour later. These effects were dose-dependent with respect to the amount of anti-insulin serum administered. The simultaneous administration of glucagon with anti-insulin serum at birth was no more effective in mobilising glycogen stores than anti-insulin serum alone, although plasma glucose concentrations in these animals were higher and plasma lactate concentrations were lower. Either anti-insulin serum or glucagon abolished the postnatal hypoglycaemia observed in untreated neonatal rats. The rate of fall in plasma lactate concentrations after birth was stimulated in glucagon-treated rats but was retarded in rats treated with anti-insulin serum. Hormonal control over the initiation of glycogenolysis and gluconeogenesis in the newborn rat appears to be different, a fall in plasma insulin being the prime factor involved in triggering glycogen mobilization and a rise in plasma glucagon the prime event that initiates gluconeogenesis.

Animals↗

Role of exotoxin and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa.

Evidence is presented which suggests that both the proteases and the exotoxin produced by Pseudomonas aeruginosa multiplying in situ in a burned mouse model are virulence factors. A 50% decrease in functional elongation factor 2 (EF-2) was seen 16 h postinfection in the liver of mice infected with the toxigenic, protease-producing P. aeruginosa strain M-2; at the time of death EF-2 was depleted by 80%. This correlates with a reduction in the level of protein synthesis in the liver of infected animals. Treatment with specific antitoxin extended the mean time to death and blocked depletion of EF-2. Administration of gentamicin 24 h after infection caused rapid clearance of bacteria and extended the mean time to death, but all animals treated with either antitoxin or gentamicin eventually died. In contrast, treatment with both antitoxin and gentamicin provided virtually complete protection. Infection of mice with P. aeruginosa WR5 (protease-producing, nontoxigenic) or with P. aeruginosa PA103 (toxigenic, slow protease producer) required several logs more bacteria and did not result in the same extensive depletion in EF-2 content. When challenge with PA103 was supplemented by injection of purified Pseudomonas protease, the mean time to death was shortened and significant reduction in liver EF-2 was observed. It is suggested that both toxin and proteases are required for the full expression of virulence in Pseudomonas infections.

Animals↗

The release of alanine by rat diaphragm muscle in vitro.

Alanine release by rat diaphragm muscle in vitro is stimulated by glutamate, valine, leucine and glucose. The stimulation by glutamate and valine (but not leucine) is inhibited by 3-mercaptopicolinate. These results suggest a metabolic route involving phosphoenolpyruvate carboxykinase which directs amino acid carbon skeletons towards pyruvate synthesis for alanine formation.

Alanine↗

Experimental studies on the pathogenesis of infections due to Pseudomonas aeruginosa: direct evidence for toxin production during Pseudomonas infection of burned skin tissues.

Direct evidence is presented for the production of an exotoxin by Pseudomonas aeruginosa multiplying at the burned site in an infected mouse. Pseudomonas toxin was assayed by measurement of its ability to catalyze the transfer of radioactivity from [14C]adenine-labeled nicotinamide adenine dinucleotide to elongation factor 2 (adenosine diphosphate ribosylation activity). This enzyme activity was found in saline extracts of burned infected skin but was not present in similar extracts of burned uninfected skin. It was detected in the serum of infected animals by 26 hr after infection. The level of active elongation factor 2 in the livers of infected mice was reduced significantly after infection. These data suggest that pseudomonas exotoxin, produced by bacteria multiplying at the burn site, enters the circulation and is disseminated to different organs where it acts by depletion of elongation factor 2 and thus causes a reduction in protein synthesis.

Animals↗

Pathways of gluconeogenesis from L-serine in the neonatal rat.

Gluconeogenesis from amino acid precursors was increased in the perfused liver of neonatal rats compared with that of adults. Quinolinate (5mm) was less inhibitory to glucose formation from serine and hydroxyproline in the neonatal rat than in the adult, suggesting that the main route for glucose synthesis from these precursors in neonatal liver does not involve pyruvate as an intermediate.

Animals↗

Regulation of hepatic L-serine dehydratase and L-serine-pyruvate aminotransferase in the developing neonatal rat.

1. The activities of l-serine dehydratase and l-serine-pyruvate aminotransferase were determined in rat liver during foetal and neonatal development. 2. l-Serine-pyruvate aminotransferase activity begins to develop in late-foetal liver, increases rapidly at birth to a peak during suckling and then decreases at weaning to the adult value. 3. l-Serine dehydratase activity is very low prenatally, but increases rapidly after birth to a transient peak. After a second transient peak around the time weaning begins, activity gradually rises to the adult value. Both of these peaks have similar isoenzyme compositions. 4. In foetal liver both l-serine dehydratase and l-serine-pyruvate aminotransferase activities are increased after injection in utero of glucagon or dibutyryl cyclic AMP. Cycloheximide or actinomycin D inhibited the prenatal induction of both enzymes and actinomycin D blocked the natural increase of l-serine dehydratase immediately after birth. Glucose or insulin administration also blocked the perinatal increase of l-serine dehydratase. 5. After the first perinatal peak of l-serine dehydratase, activity is increased by cortisol and this is inhibited by actinomycin D. After the second postnatal peak, activity is increased by amino acids or cortisol and this is insensitive to actinomycin D inhibition. Glucose administration blocks the cortisol-stimulated increase in l-serine dehydratase and also partially lowers the second postnatal peak of activity. 6. The developmental patterns of the enzymes are discussed in relation to the pathways of gluconeogenesis from l-serine. The regulation of enzyme activity by hormonal and dietary factors is discussed with reference to the changes in stimuli that occur during neonatal development and to their possible mechanisms of action.

Animals↗

Glucose metabolism in the newborn rat. Temporal studies in vivo.

1. The concentrations of plasma d-glucose, l-lactate, free fatty acids and ketone bodies and of liver glycogen were measured in caesarian-delivered newborn rats at time-intervals up to 4h after delivery. Glucose and lactate concentrations decreased markedly during the first hours after delivery, but there was a delay of 60-90min before significant glycogen mobilization occurred. 2. The specific radioactivity of plasma d-glucose was measured as a function of time for up to 75min after the intraperitoneal injection of d-[6-(14)C]glucose and d-[6-(3)H]glucose into caesarian-delivered rats at 0, 1 and 2h after delivery. Calculations revealed that there was an appreciable rate of glucose formation at all ages studied, but immediately after delivery this was exceeded by the rate of glucose utilization. Around 2h post partum the rate of glucose utilization decreased dramatically and this coincided with a reversal of the immediately postnatal hypoglycaemia. 3. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose and liver glycogen was measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into rats immediately after delivery. The logarithm of the specific radioactivity of plasma l-[U-(14)C]lactate decreased linearly with time for at least 60min after injection and the calculated rate of lactate utilization exceeded the rate of lactate formation. 4. (14)C incorporation into plasma d-glucose was maximal from 30-60min after injection of l-[U-(14)C]lactate and the amount incorporated at 60min was 23% of that present in plasma lactate. Although (14)C was also incorporated into liver glycogen the amount was always less than 3% of that present in plasma glucose. 5. The results are discussed in relationship to the adaptation of the newly born rat to the extra-uterine environment and the possible involvement of gluconeogenesis at this time before feeding is established.

Acetoacetates↗

Glucose metabolism in the newborn rat. Hormonal effects in vivo.

1. The concentrations of liver glycogen and plasma d-glucose were measured in caesarian-delivered newborn rats at time-intervals up to 3h after delivery after treatment of the neonatal rats with glucagon, dibutyryl cyclic AMP, cortisol or cortisol+dibutyryl cyclic AMP. Glycogenolysis was promoted by glucagon or dibutyryl cyclic AMP in the third hour after birth but not at earlier times. Cortisol and dibutyryl cyclic AMP together (but neither agent alone) promoted glycogenolysis in the second hour after birth, but no hormone combination was effective in the first postnatal hour. 2. The specific radioactivity of plasma d-glucose was measured as a function of time for up to 75 min after the intraperitoneal injection of d-[6-(14)C]glucose and d-[6-(3)H]glucose into newborn rats at delivery and after treatment with glucagon or actinomycin D. Glucagon-mediated hyperglycaemia at this time was due to an increased rate of glucose formation and a decreased rate of glucose utilization. Actinomycin D prevented glucose formation and accelerated the rate of postnatal hypoglycaemia. 3. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose was measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into glucagon- or actinomycin D-treated rats immediately after delivery. The calculated rates of lactate formation were unchanged by either treatment, but lactate utilization was stimulated by glucagon administration. Glucagon stimulated and actinomycin D diminished (14)C incorporation into plasma d-glucose. 4. The factors involved in the initiation of glycogenolysis and gluconeogenesis in the rat immediately after birth are discussed.

Animals↗