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A Bruce-Robertson

Publications and source records attributed to A Bruce-Robertson.

14 recordsLinked to original sources
PubMed1980

Hepatotrophic effects of insulin on glucose, glycogen, and adenine nucleotides in hepatocytes isolated from fed adult rats.

In vivo observations have suggested that there is an hepatotrophic effect of insulin. By contrast, subsequent in vitro work, using the isolated perfused liver system, showed no effect or indeterminate effects of insulin on the transport of glucose into the hepatocyte. However because this system may not have endured long enough to show such an influence we explored the transport of glucose using a 48-h suspension culture of hepatocytes isolated from young adult fed rats, the suspension being infused continuously with insulin at a rate approximating the maximum entering portal blood in the fed state. (In a separate study phloridzin was added after 2 h of incubation.) DNA, intracellular glucose and its inward transport, glycogen, and the adenine nucleotides were measured at intervals. By comparison with control or untreated cells, insulin-treated cells showed significantly more DNA and intracellular glucose, and the differences were abolished by phloridzin. Glucose transport rates fell to low values in untreated controls and still lower with insulin plus phloridzin, but the initial rate was maintained to the end (48 h) by insulin alone. Results for glycogen were similar to those for intracellular glucose. There was a close correlation (r = 0.96) between these two. The total adenine nucleotide pool and the concentration of ATP were maintained for about 24 h and fell to half their initial values by 48 h. Insulin had increased these concentrations significantly by 6 h. Although concentrations of ADP and AMP decreased gradually in all groups of cells, insulin enhanced the level of ADP by 12 h but had no measurable effect on that of AMP. The energy charge increased slightly throughout incubation but more so (by 6 h) in the presence of insulin. In conclusion the data support the concept that in the longer term (greater than 12 h) insulin in the portal circulation maintains the characteristic free permeability of the hepatocyte to glucose and this permits a variety of effects related to glucose entry into the hepatocyte.

Adenine Nucleotides↗
PubMed1980

Hepatotrophic effects of insulin on glucose, glycogen, and adenine nucleotides in hepatocytes isolated from fasted adult rats.

Previous evidence that portal blood insulin is an hepatotrophic factor led to this study of its effect on hepatocytes, isolated from fasted rats, in suspension culture. Control hepatocytes (C), noninsulin-treated, and those infused continuously at low (LI) and high (HI) levels of insulin were compared concurrently with regard to their survival, glucose transport, and intracellular concentrations of glucose, glycogen, and adenine nucleotides, over a 48-hr period of incubation. Low insulin was adjudged to be comparable to portal insulin concentrations in fasted animals and HI to those in fed animals. All hepatocytes had been depleted of glucose, glycogen, and adenine nucleotides at the start of the study by prior fasting of the rat. For the first 6 hr of culture, there was little difference between C, LI, and HI with reference to the above parameters. In contrast, after 48 hr of incubation, cell survival, as judged by the DNA content, was signficiantly lower in C compared with LI and HI. The transport of 3--0-[methyl-3H] D-glucose was also significantly lower in C compared with LI and HI. The higher uptakes in both LI and HI were reduced by phloridzin, which had little effect on C. Correspondingly, the intracellular glucose concentrations in C were significantly lower than the extracellular glucose concentrations in contrast to those in LI and HI, which were comparable. For intracellular concentrations of glycogen and adenine nucleotides, the results of LI and HI were amalgamated as they were not significantly different from each other at 48 hr. Upon analysis, glycogen values were significantly higher for insulin-treated cells. Similarly, the total adenine nucleotide p-ol (ATP + ADP + AMP) also was clearly higher in HI + LI than in C. These results indicate that contrary to findings in studies with the perfused liver that have been of a short-term nature, insulin is necessary in the longer term (greater than 12 hr) for maintaining the transport of glucose into hepatocytes; thereby insulin promotes the maintenance of intracellular glucose, glycogen, and adenine nucleotide concentrations, and also enhances cell survival.

Adenine Nucleotides↗
PubMed1977

Effects of hormones on the synthesis of alpha 1 (acute-phase) glycoprotein in isolated rat hepatocytes.

Hormone effects on the synthesis of alpha(1) (acute-phase) glycoprotein and of albumin by isolated rat hepatocytes in suspension were examined. Insulin, glucagon, cortisol, somatotropin (bovine growth hormone) and tri-iodothyronine were added to achieve physiological concentrations in the medium [Jeejeebhoy, Ho, Greenberg, Phillips, Bruce-Robertson & Sodtke (1975) Biochem. J.146, 141-155]. After periodic additions, there were increases (compared with values for non-hormone-treated suspensions) in the concurrent absolute syntheses of alpha(1) (acute-phase) glycoprotein and of albumin. Trends were detectable after 24h, and significant increases were demonstrated after 48h of incubation (219 and 119% respectively of control values). Manipulation of hormones, by omission from the mixture or by addition of only one or two hormones in various combinations, indicated that for alpha(1) (acute-phase) glycoprotein (which may be representative of some other acute-phase proteins), cortisol was one of the most important hormones involved in the stimulation of synthesis, with glucagon enhancing the effect of cortisol but not being stimulatory by itself. Addition of actinomycin D inhibited this stimulation, suggesting that cortisol might have acted through promotion of RNA synthesis. For albumin, cortisol alone did not stimulate synthesis, but its absence from a hormone mixture significantly decreased synthesis compared with that observed with the complete hormone mixture. Our findings support the possibility that following tissue injury, synthesis of alpha(1) (acute-phase) glycoprotein may be stimulated by the hormonal response to this injury (which response includes elevated blood concentrations of cortisol and glucagon).

Albumins↗
PubMed1977

Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition.

A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.

Adult↗
PubMed1976

Synthesis of hemopexin with and without hormonal supplementation in rat hepatocyte suspensions: comparison with that of albumin and of fibrinogen.

The rate of hemopexin synthesis in adult rat hepatocyte suspension (0.17 +/- 0.019 (6)) (mean +/- SEM (n) mg/g hepatocytes per hour) was found to be linear for 48 h. By contrast, the rate of synthesis of albumin and fibrinogen was close to linear for only 12 h after which it continued at a diminished rate. Supplementation of the incubation medium with insulin, cortisol, glucagon, triiodothyronine, and growth hormone affected no significant increase in the synthesis rate of hemopexin but by contrast did do so in that of albumin (22%) and of fibrinogen (123%) (although not to the point of causing these last to become linear). The pattern of hemopexin synthesis and its response to hormones is clearly different from that observed with other plasma proteins studied in this hepatocyte system. Hempoexin synthesis appeared to be at its maximum and to be independent of hormone supplementation, and it was continuing linearly at a time when the synthesis of other plasma proteins was falling.

Albumins↗
PubMed1975

Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis.

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.

Adenosine Triphosphate↗
PubMed1972

The acute effect of ethanol on albumin, fibrinogen and transferrin synthesis in the rat.

Decrease of absolute synthesis of albumin and fractional synthesis of transferrin was observed within 3h of orally administering ethanol (4ml/kg) to rats maintained on a 40%-protein diet. In contrast, absolute synthesis of fibrinogen was unaffected. With this ethanol intake, the changes in protein synthesis occurred without significant ultrastructural change in the liver. When the ethanol intake was greater (8ml/kg) ultrastructural disruption was observed. However, both the decrease of plasma protein synthesis and the ultrastructural alterations could be prevented by the simultaneous administration of a mixture of amino acids with the ethanol. The latter findings, not reported hitherto, suggest that ethanol may interfere with hepatic plasma protein synthesis and ultrastructure more through a disturbance of amino acid metabolism than through direct physical damage to the hepatocyte. An Appendix outlines the deconvolutional method used to correct for losses of labelled protein in the period during which measurements were made. The principle may also be applied to labelled plasma urea. The details of the calculations are given in a supplementary paper that has been deposited as Supplementary Publication 50007 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1972) 126, 5.

Administration, Oral↗
PubMed1972

The effect of cortisol on the synthesis of rat plasma albumin, fibrinogen and transferrin.

A decrease of absolute synthesis of albumin, no change in that of fibrinogen and an increased fractional synthesis of transferrin were observed 3h after intraperitoneal administration of a pharmacological dose of 5 mg of cortisol to 220g rats in the post-absorptive state and previously kept on a diet with 40% protein. The concentration in liver of total free amino acids was practically unchanged at this time. Intraperitoneal administration of a mixture of amino acids with the cortisol raised this concentration and was accompanied by an almost complete de-repression of the synthesis of albumin, with no real effect on that of fibrinogen. In considerable contrast, in rats studied at 24h after intraperitoneal administration of cortisol, and who had been fed once in the interim (but who had received no amino acids intraperitoneally), there was a marked increase in the absolute synthesis of albumin and fibrinogen, with an increase in fractional synthesis that was less proportionately but still very significant and which included transferrin. The amino acid concentrations had risen above the supplemented values at 3h but not as much proportionately as the fractional synthesis rates, and of course not as much as the absolute synthesis rates, of albumin and fibrinogen. These time-dependent effects of cortisol suggest to us that our studies resolve the apparently conflicting results of the effect of cortisol on the synthesis of albumin reported by others.

Amino Acids↗
PubMed1970

The effect of growth hormone on fibrinogen synthesis.

A method described by McFarlane (1963a) for the measurement of the absolute rate of synthesis of liver-made plasma proteins was used to show that, within a few hours of giving bovine growth hormone to rats, fibrinogen synthesis increased significantly without a change in albumin synthesis.

Animals↗