Beta cell response to the hyperglycaemic clamp in three patients with insulinoma: a study using a hyperglycaemic glucose clamp

To determine the mechanism responsible for deficient carbohydrate metabolism in patients with insulinoma, we studied three affected patients and seven normal controls using the hyperglycaemic clamp method (8.4 mmol/l) with the BIOSTATOR (GCIIS). In insulinoma patients, the amount of glucose necessary to reach the hyperglycaemic clamp was less than that required in normal controls (6.19 +/- 1.19 mg/min/kg vs. 9.95 +/- 0.53 mg/min/kg) (p less than 0.05). There was no significant difference in metabolized glucose (M) in the stable phase of the hyperglycaemic clamp; however, the M/IRI in this phase was less in those with insulinoma (7.9 +/- 0.50) than in controls (22.26 +/- 4.14) (p less than 0.05). There was no difference in beta cell secretory response to hyperglycaemic stimulus (defined as the increase in the concentration of C-peptide from the basal state to the stable phase of the hyperglycaemic clamp) between the two groups. Hepatic insulin extraction was significantly lower in patients with insulinoma than in normal controls (+0.72 +/- 0.07 vs. +0.85 +/- 0.01). Finally, the ratios of fractional turnover of glucose (K/IRI); glucose clearance/IRI and total rate of elimination of glucose from the extracellular pool/IRI were also all lower in patients with insulinoma than in controls (p less than 0.05). These data support the conclusion that deficient glucose metabolism seen in these patients is not related to a lack of response to glucose on the part of normal or neoplastic islet tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of endogenous free amino acids in rabbit reticulocyte lysates and the effect of incubation

Amino acid analyses show that while the free amino acids found in the rabbit reticulocyte translation system do not increase during nuclease treatment or during prolonged storage, the endogenous levels of many amino acids are so high that the choice of a radioactive; precursor for a translation should be based not only on the abundance of the amino acid in the translation product but also on its concentration in the lysate preparation. It is shown that the variation of amino acid concentrations between different lysates is sufficiently small to allow one to use the concentrations reported in this study to calculate the amount of radioactive amino acid necessary for satisfactory incorporation.     

Optical properties of cyclic dimers of amino acids: An experimental and theoretical study

CD spectra have been measured in the vacuum-uv region to about 135 nm for cyclo(L alanyl-glycine), cyclo(L alanyl-L -alanine), and cyclo(L -prolyl-L -proline). In addition to the amide CD bands usually observed at wavelengths longer than 180 nm, a Independent systems calculations show that these intense short-wavelenght bands can be attributed to σσ* transitions of the backbone. Transitions of the amide chromophore expected at wavelenghts shorter than 180 nm cannot account for the observed CD.     

Effects of intra-abomasal infusion of beta-casomorphins on circulating concentrations of hyperglycaemic insulin and glucose in dairy cows

The effects of intra-abomasal infusion of a mixture of -casomorphins on circulating concentrations of insulin and glucose prestimulated by either abomasal (experiment 1) or intravenous (experiment 2) glucose were studied using non-lactating dairy cows. In both experiments, bolus infusion of 240 mg of a mixture of three beta-casomorphins (beta-casomorphin-4-amide, -5 and -7) was given via an abomasal infusion line. The beta-casomorphins significantly lowered the responses of serum insulin to both abomasal and intravenous glucose infusions (P<0.05). However, the beta-casomorphins did not significantly affect circulating glucose concentrations. The insulinopenic action of the beta-casomorphins is consistent with the action of somatostatin-28 (SS-28) as judged from the effects of SS-28 on the insulin secretion when administered intravenously in experiment 1.     

Incorporation of amino acids into protein of foetal rabbit diaphragm: effect of insulin.

The incorporation of six L-amino acids into the protein fraction of the diaphragm of foetal and neonatal rabbits has been measured. Insulin stimulates the incorporation of lysine from the 29th day and of glycine from the 31st day of gestation onwards. The incorporation of histidine, serine and threonine is only enhanced in the diaphragm of 16-20 hour-old rabbits; no effect of insulin on the incorporation of leucine has been shown for the period under study.     

The effect of unilateral partial facial paralysis on nasofrontal sutural growth: an experimental study in the rabbit.

In a previous study in the rabbit, it was demonstrated that paralysis of the midfacial musculature results in decreased anteroposterior growth of the snout. At the end of growth, these animals showed macroscopically striking similarities to animals with unilateral fusion of the nasofrontal suture. In this study, whether nasofrontal sutural growth is unilaterally restricted in animals with unilateral partial facial paralysis was investigated. A left-sided partial facial paralysis was induced in sixteen 12-day-old New Zealand White rabbits. At the ages of 5, 9, 12, and 17 weeks, four animals were randomly assigned to be killed for analysis of nasofrontal sutural growth. In each animal, the left experimental side was compared with the right control side. By means of histomorphometric measurements, it was shown that diminished sutural growth activity was present on the left paralyzed side in periods of rapid growth. On the other hand, no significant alterations in sutural width were found. These findings seem to explain some of the macroscopic growth alterations (i.e., diminished anterior maxillary length) observed in rabbits with unilateral partial facial paralysis.     

Free amino acids in the early cleavage stages of the rabbit egg

In the first half of gestation, mouse yolk sac contains levels of N-acetyl-β-hexosaminidase activity and a ratio of N-acetyl-β-hexosaminidase: β-glucuronidase much higher than those of other embryonic tissues or the decidua. The properties of the yolk sac enzyme are very similar to those in the other tissues, suggesting that the observed difference in activity is quantitative rather than qualitative. In blastocyst cultures, the vesicular growths derived from the inner cell mass possess patterns of N-acetyl-β-hexosaminidase activity similar to yolk sac in vivo, but different from trophoblast cells developing in the same cultures. It is therefore proposed that the vesicular growths contain at least some differentiated yolk sac cells.     

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ～12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min(-1)·kg(-1), P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min(-1)·kg(-1) in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min(-1)·kg(-1) in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min(-1)·kg(-1) in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg(-1)·min(-1), P < 0.05). The glucose-O(2) quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r(2) = 0.38, P < 0.05), cortisol (r(2) = 0.31, P < 0.05), and NE (r(2) = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids.     

Synchronising the availability of amino acids and glucose increases protein retention in pigs

Effects of synchronising the availability of amino acids and glucose within a day on protein and energy metabolism were studied in growing pigs. Ten pigs of on average 54 (s.e. 1.0) kg live weight were assigned to each of two dietary treatments (synchronous v. asynchronous nutrient supply) in a change-over design. On the synchronous treatment (SYN), pigs received two balanced meals: one at 0800 h and one at 1600 h. On the asynchronous treatment (ASYN), pigs received virtually all protein at 0800 h and all carbohydrates at 1600 h. The dietary supply of ingredients and nutrients to pigs was similar for both treatments. Pigs were housed individually in respiration chambers. Faecal apparent nutrient digestibility was determined and nitrogen and energy balances were measured. Faecal apparent digestibility of energy, organic matter and non-starch polysaccharides was higher ( P < 0.05) for SYN than for ASYN. The efficiency of utilisation of digestible protein with protein gain was higher ( P = 0.001) for SYN (56.7%) than for ASYN (47.1%). The substantial decrease ( P < 0.05) in respiratory quotient and ¹³C enrichment of the expired CO₂ after the morning meal indicated higher amino acid oxidation for ASYN than for SYN. Heat production and energy retention as fat were not affected by nutrient synchrony. In conclusion, an asynchronous availability of glucose and amino acids within a day increases amino acid oxidation, resulting in a substantial reduction in protein utilisation but with virtually no effect on fat retention.     

Utilization of glucose and amino acids byBacteroides intermedius andBacteroides gingivalis

Growth ofBacteroides intermedius was promoted only moderately by glucose, and the incorporation of¹⁴C-glucose into cells was limited. WithBacteroides gingivalis growth promotion was negligible and glucose incorporation even more restricted. Both species grew prolifically on protein hydrolysates containing peptides, but grew poorly on acid-hydrolyzed casein even when supplemented with amino acids. These results are discussed in relation to the ecological distribution of these species compared to saccharolytic bacteroides.     

Ventriculo–cisternal perfusion of twelve amino acids in the rabbit

The clearances of twelve amino acids from the ventricles during ventriculocisternal perfusion in the rabbit have been measured; uptake by the brain was also measured and this permitted the separate computation of loss to brain and loss to blood during the perfusion. Clearance under carrier-free conditions was greater than when a concentration of 5mM unlabeled amino acid was present in the perfusion fluid. Brain uptake was also usually reduced by the presence of unlabeled amino acid due presumably to suppression of accumulation by brain cells. Reduction of transport across the blood-brain barrier would tend to increase brain uptake, and there was some evidence for a balance between the two opposing tendencies. Inhibition of clearance of a given labeled amino acid could be brought about by unlabeled amino acids of different molecular species. In general, the amino acids fell into three categories: neutral, acidic, and basic, and there was some overlap between them; of the neutral amino acids the A- and L-classification of Christensen was valid, although once again there was some overlap. If, during ventriculo-cisternal perfusion of a labeled amino acid, the activity of this labeled amino acid in the blood was raised well above that in the inflowing perfusion fluid, the labeled amino acid continued to be cleared from the perfusion fluid, suggesting uphill transport. On this basis it was suggested that the normally low concentrations of amino acids in the cerebrospinal fluid (CSF), by comparison with those in plasma, were due to an active transport from the CSF to the blood. Substrate-facilitated transport, whereby the penetration of labeled amino acid into the perfusion fluid from blood could be accelerated by adding unlabeled amino acid to the perfusion fluid, or vice versa, was demonstrated.