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Biomedical subjects

P Felig

Publications and source records attributed to P Felig.

231 records · Page 13Linked to original sources
PubMed1969

Amino acid metabolism during prolonged starvation.

Plasma concentration, splanchnic and renal exchange, and urinary excretion of 20 amino acids were studied in obese subjects during prolonged (5-6 wk) starvation. Splanchnic amino acid uptake was also investigated in postabsorptive and briefly (36-48 hr) fasted subjects.A transient increase in plasma valine, leucine, isoleucine, methionine, and alpha-aminobutyrate was noted during the 1st wk of starvation. A delayed, progressive increase in glycine, threonine, and serine occurred after the 1st 5 days. 13 of the amino acids ultimately decreased in starvation, but the magnitude of this diminution was greatest for alanine which decreased most rapidly during the 1st week of fasting. In all subjects alanine was extracted by the splanchnic circulation to a greater extent than all other amino acids combined. Brief fasting resulted in an increased arterio-hepatic venous difference for alanine due to increased fractional extraction. After 5-6 wk of starvation, a marked falloff in splanchnic alanine uptake was attributable to the decreased arterial concentration. Prolonged fasting resulted in increased glycine utilization by the kidney and in net renal uptake of alanine. It is concluded that the marked decrease in plasma alanine is due to augmented and preferential splanchnic utilization of this amino acid in early starvation resulting in substrate depletion. Maintenance of the hypoalaninemia ultimately serves to diminish splanchnic uptake of this key glycogenic amino acid and is thus an important component of the regulatory mechanism whereby hepatic gluconeogenesis is diminished and protein catabolism is minimized in prolonged fasting. The altered renal extraction of glycine and alanine is not due to increased urinary excretion but may be secondary to the increased rate of renal gluconeogenesis observed in prolonged starvation.

Adolescent↗
PubMed1969

Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels.

Amino acid balance across skeletal muscle and across subcutaneous adipose tissue plus skin of the forearm has been quantified in postabsorptive man before and after insulin infusion into the brachial artery. Skeletal muscle released significant amounts of alpha amino nitrogen after an overnight fast. Most individual amino acids were released. Alanine output was by far the greatest. The pattern of release probably reflects both the composition of muscle protein undergoing degradation and de novo synthesis of alanine by transamination. A significant correlation was observed between the extent of release of each amino acid and its ambient arterial concentration. Elevation of forearm insulin in eight subjects from postabsorptive (12 muU/ml) to high physiologic levels (157 muU/ml) in addition to stimulating muscle glucose uptake blocked muscle alpha amino nitrogen release by 74%. Consistent declines in output were seen for leucine, isoleucine, tyrosine, phenylalanine, threonine, glycine, and alpha-aminobutyric acid. Alanine output was insignificantly affected. Doubling forearm insulin levels (from 10 to 20 muU/ml) in eight subjects increased muscle glucose uptake in three and blocked alpha amino nitrogen output in two although both effects were seen concurrently in only one subject. Changes in net amino acid balance after insulin could be accounted for by increased transport of amino acids into muscle cells or retardation of their exit. It is likely that ambient arterial amino acid concentrations are established and maintained primarily by the extent of muscle amino acid release. The individual amino acids whose outputs from forearm muscle decline after forearm insulinization correspond well with those whose levels fall systematically after systemic insulinization. This suggests that declines in amino acid levels after systemic insulinization are due to inhibition of muscle release. Doubling basal insulin approaches the threshold both for blockade of muscle amino acid output and stimulation of glucose uptake, effects which appear to occur independently.

Adipose Tissue↗
PubMed1965

Changes in hepatic structure in rats produced by breathing pure oxygen.

The livers of rats exposed to pure oxygen were examined electron microscopically to study toxic effects of oxygen in a metabolically sensitive organ. Pressures of 1/3 (258 mm Hg), 1 (760 mm Hg), and 3 (2280 mm Hg) atmospheres were used, with exposures up to 90 days with the lowest pressures. The first changes in the hepatocytes were loss of glycogen and enlargement of mitochondria with development of mitochondria with bizarre shapes which were seen after 3 days at 258 mm, 1 day at 760 mm, and 3 hours at 2280 mm. These changes were followed by formation of increased numbers of cristae, membranes surrounding mitochondria, autophagic vacuoles, and polyribosome clusters. After 2 weeks at 258 mm, which is the pressure of the atmosphere of space cabins, numerous mitochondrial myelin figures appeared but the mitochondrial enlargement had begun to regress. After 90 days at 258 mm, the liver cells appeared almost normal except that many pigment granules had accumulated in the pericanalicular zones. The changes were non-specific and seemed to parallel biochemical alterations recorded elsewhere. They are not considered the result of toxicity but rather of adaptation. These atmospheres, which are used in clinical medicine and in space travel, appear to have no permanent deleterious effects on the liver in rats under the conditions of this experiment.

Adaptation, Physiological↗
PubMedDate not supplied

Influence of L-leucine on glutamate dehydrogenase activity in isolated rat diaphragm.

Glutamate dehydrogenase (NAD) activity was measured in liver and diaphragm mitochondria from 48 h fasted rats. Kinetic studies were performed with diaphragm enzyme and the effects of L-leu, ADP and L-ala on the K(1)m and V(1)max for NH(4)+, and α-ketoglutarate were evaluated. L-leucine increases by 2-8 fold the V(1)max for all three substrates with no significant changes in the K(1)m. ADP increased by 3-7 fold the V(1)max for all three substrates and the K(1)m for NADH and α-ketoglutarate by 1.5-7.0 fold. L-alanine had no effect on either the V(1)max or the K(1)m of any substrate. The results suggest that muscle has the capacity to form glutamate through the glutamate dehydrogenase reaction and that L-leucine may stimulate this reaction in muscle.

Alanine↗
PubMedDate not supplied

Circulatory and temperature regulatory responses to exercise in a warm environment in insulin-dependent diabetics.

Because diabetics are prone to the development of neuropathy and microvascular disease, abnormalities of cardiovascular reactivity and capillary permeability in response to acute exercise and/or an increase in environmental temperature might presage the development of clinically overt complications. In the present study insulin-dependent diabetics without evidence of microangiopathy or neuropathy and controls matched for the same level of physical fitness performed cycle ergometer exercise for 20 minutes at 65 percent VO2 max in a temperature maintained at 35 percent C. Ther rise in heart rate (82-85 beats min-1), the fall in plasma volume (11-13 percent), and the increase in total serum proteins (13-16 percent) induced by exercise were the same in the two groups. Furthermore, comparable increments in skin blood flow (two- to threefold) and in core and skin temperatures were observed. The relationship between increases in body core temperature and increases in skin blood flow and the vasodilatory threshold (37.0 percent C) were also the same in the diabetics and controls.

Adult↗
PubMedDate not supplied

Long-term improvement of metabolic control with the insulin pump does not reverse diabetic microangiopathy.

Restoration of near-normal glucose metabolism with the insulin pump reduces retinal fluorescein leakage and microalbuminuria in diabetes. However, it is not known whether these functional changes reflect a true reversal of diabetic retinopathy or nephropathy. To evaluate this question, we studied the effect of 1-2 yr of insulin pump treatment on clinical endpoints in 17 type I diabetic patients. In each patient, plasma glucose and total glycosylated hemoglobin levels fell to normal or near-normal levels. The total daily dose of insulin given during the first month of pump treatment (52 +/- 5 U/day) was comparable to that given during conventional treatment (44 +/- 3 U/day) and varied little over the 1-2 yr period of observation. Ten eyes without retinopathy at the start of the study remained without retinopathy after 15-23 mo of pump treatment. One of eleven eyes with background retinopathy developed proliferative retinopathy and 3 of 13 eyes with proliferative retinopathy progressed during pump treatment. Similarly, no improvement in renal function was observed in the six patients with diabetic nephropathy on entry to the study. In the first month of pump treatment, proteinuria consistently fell to values 30% below prepump levels (P less than 0.005). However, the diminution in proteinuria was not sustained and all remain proteinuric after 13-18 mo of pump therapy. Serum creatinine rose slightly and creatinine clearance did not significantly change. These data suggest that insulin pump treatment does not reverse established diabetic microvascular complications, despite a sustained improvement in metabolic control for up to 2 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗