Biomedical subjects

G Lippe

Publications and source records attributed to G Lippe.

25 records · Page 2Linked to original sources

PubMed1986

Type I diabetes is characterized by insulin resistance not only with regard to glucose, but also to lipid and amino acid metabolism.

Resistance to the metabolic effects of insulin has been reported with regard to glucose disposal in type I diabetic patients (IDDM) even when they were euglycemic. Our aim was to study glucose, lipid, and amino acid metabolism during glucose clamping at multiple levels of insulin in 10 normal (N) and 6 IDDM patients. Blood glucose was maintained constant (4.7 mmol/liter) at three insulin plateaus (160 min each) [42 +/- 6 (SD) 89 +/- 11, and 1255 +/- 185 microU/ml in N and 36 +/- 4, 80 +/- 13, and 1249 +/- 107 microU/liter in IDDM]. Mean glucose disposal was 34 +/- 11, 69 +/- 10, and 84 +/- 22 mumol kg-1 min-1 in N and 16 +/- 5, 40 +/- 18, and 65 +/- 27 in IDDM, respectively. Baseline concentrations of blood lactate, pyruvate, alanine, and branched chain amino acids were 560 +/- 130, 36 +/- 9, 212 +/- 44, and 451 +/- 19 mumol/liter, in N and 793 +/- 179 (P less than 0.05), 45 +/- 14, 195 +/- 50, and 439 +/- 33 in IDDM, respectively. The maximum percent change of lactate during the euglycemic clamp was +147 +/- 23% in N and +75 +/- 15% (P less than 0.05) in IDDM; that of branched chain amino acids was -61 +/- 5% in N and -48 +/- 7% (P less than 0.01) in IDDM. Baseline concentrations of glycerol, FFA, and adipate were 44 +/- 15, 449 +/- 152, and 8 - 8 mumol/liter in N and 39 +/- 14, 473 +/- 44, and 41 +/- 14 (P less than 0.01) in IDDM. The maximum percent change of glycerol during the euglycemic clamp was -50 +/- 8% in N and -16 +/- 8% (P less than 0.01) in IDDM, that of FFA -98 +/- 3% in N and -70 +/- 4% in IDDM (P less than 0.05). No significant differences were found between N and IDDM with regard to blood concentrations of ketone bodies, citrate, ketoglutarate, and hydroxymethylglutaryl coenzyme A both before and during the euglycemic clamp. The lactate percent increase was significantly correlated to glucose disposal rate (P less than 0.001). The lactate turnover rate increased during the euglycemic clamp and was lower in IDDM than in N. We conclude that during euglycemic-multiple insulin clamp studies the greater lactate increase suggests that the flux of glycolysis is higher in N than in IDDM, tricarboxylic acid concentrations are comparable in N and IDDM, and FFA, glycerol, and branched chain amino acid decreases were less in IDDM than in N, suggesting that IDDM patients are resistant to insulin with regard to lipid and protein metabolism. The higher adipate basal values demonstrate enhanced omega-oxidation in IDDM.

Adult↗

PubMed1985

Current-voltage relationships for proton flow through the F0 sector of the ATP-synthase, carbonylcyanide-p-trifluoromethoxyphenylhydrazone or leak pathways in submitochondrial particles.

Respiring submitochondrial particles from which the F1 sector of ATP-synthase was displaced generated a membrane potential in the range of 115-140 mV. Addition of oligomycin raised the membrane potential by approximately 40 mV. The lower membrane potential in particles with F1 displaced is attributed to partial dissipation of the proton electrochemical gradient as a consequence of proton flow through the open proton channels provided by the F0 sectors of the ATP-synthase. The characteristics of proton flow through the open F0 channels were studied by varying the rate of electron transport-driven proton translocation which permitted the establishment of a range of steady-state membrane potentials. Open F0 channels appeared to have a gated response to the membrane potential such that they were inoperative when the potential fell below approximately 110 mV. The membrane potential was measured as a function of respiratory rate in intact Mg-ATP submitochondrial particles that had been treated with low concentrations of the protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone. In general a linear dependence of membrane potential upon respiratory rate was observed except at the lowest concentrations of protonophore and highest respiratory rates, presumably because the effect of the protonophore was then offset by an increased rate of proton translocation driven by the respiratory chain. The effect of increasing concentrations of carbonylcyanide-p-trifluoromethoxyphenylhydrazone on the membrane potential of respiring submitochondrial particles was studied. It was found that equal amounts of the protonophore lowered the membrane potential to a lesser extent at lower values of the membrane potential. Treatment of Mg-ATP submitochondrial particles with oligomycin slightly increased (by approximately 10 mV) the size of the respiration-dependent membrane potential, but did not alter the profile of membrane potential as a function of succinate oxidation rate. The latter was controlled by titration with malonate. This result indicates that the F0 sector of the ATP-synthase does not significantly contribute to leak pathways in intact submitochondrial particles.

Adenosine Triphosphate↗

PubMed1985

Inhibition of rat liver hydroxymethylglutaryl-CoA reductase by sulfhydryl reagents, coenzyme A esters and synthetic compounds.

The activity of the microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase was assayed with a procedure based on the extraction of the product mevalonolactone in a benzene phase. Diamide is an uncompetitive inhibitor of the reaction, while coenzyme A disulfide and tetraethylthiouram disulfide act as non-competitive inhibitors. Diamide inhibition cooperatively increases with the inhibitor concentration. HMG produces a decrease in enzyme activity that combines with that of coenzyme A disulfide. Both CoASH and coenzyme A esters strongly inhibit the reductase activity. Three new synthetic compounds with either thio-ether or thio-ester groups also show inhibitory effect on the enzyme activity.

Acyl Coenzyme A↗

PubMed1985

Partial uncoupling, or inhibition of electron transport rate, have equivalent effects on the relationship between the rate of ATP synthesis and proton-motive force in submitochondrial particles.

The rates of electron transport and of ATP synthesis have been measured in bovine heart Mg-ATP submitochondrial particles oxidising succinate under conditions of partial attenuation of the proton-motive force by malonate or FCCP. This paper reports evidence that the relationship between the rate of ATP synthesis and the magnitude of the proton motive force is independent of the mode by which the decrease of the proton motive force is achieved.

Adenosine Triphosphate↗

PubMed1982

Age-dependent excretion of 3-hydroxy-3-methylglutaric acid (HMG) and ketone bodies in the urine of full-term and pre-term newborns.

Total ketone bodies and 3-hydroxy-3-methylglutaric acid (HMG) were determined in urines of full-term and pre-term newborns from the first day after birth to an age of 17. Significantly higher levels of the two catabolites were observed in the first two weeks of life of the pre-term newborns. A peak of excretion of both ketone bodies and HMG was found between the 7th and the 10th day after birth in both groups of newborns. After the 3rd month there is no significant difference between full-term and pre-term children as far as the excretion of the two analytes is concerned.

Aging↗

PubMed1982

Urinary excretion of 3-hydroxy-3-methylglutaric acid in the diabetic condition.

Urinary levels of 3-hydroxy-3-methylglutaric acid (HMG) were measured by gas-liquid chromatography (GLC) after an extraction with tetrahydrofuran in normal rats, streptozotocin-diabetic rats and starved rats. The analysis was also carried out in the urine of three diabetic patients after suspending the insulin treatment. Detectable amounts of HMG are excreted in urine by normal humans and rats and such an excretion increases in the diabetic condition. Starved rats present only traces of HMG in the urine.

Acetoacetates↗

PubMed1977

Pancreatic extract and the intestinal uptake of vitamin B12. I. Effect on the intestinal epithelium and the vitamin B12-intrinsic factor complex.

Pancreatic extract (PE) reduced the uptake of rat intrinsic factor (IF)-bound 57CoB12 by perfused rat intestinal segments (p is less than 0.02) as well as by isolated rat intestinal brush borders (p is less than 0.01). The inhibition was concentration-dependent. Preincubation of the brush borders with PE recular weight of the 57CoB12-IF complex, as well as the uptake of the complex by isolated intestinal brush borders, was unchanged after prolonged preincubation with PE. PE also inhibited the uptake of glucose by perfused intestinal segments (p is less than 0.01), but the morphology and idsaccharidase activity (p is greater than 0.5) of the intestinaleptihelium was unaltered. The results indicate that the inhibition may be due to interaction between the intestinal epithelium and PE.

Animals↗