Evaluation of Amino Acid and Protein Requirements in Chronic Uremia

Gulyassy, Paul F.; Aviram, A; Peters, John H.

doi:10.1001/archinte.1970.00310110125022

Cited by 85 publications

(30 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bilbrey et al, however, failed to observe augmented glucagon levels after protein ingestion (14). Whether the differences observed between protein ingestion and intravenous alanine are related to altered protein absorption in uremia (22), or are due to the different nature of the aminogenic stimulus remains to be determined. The present findings extend previous observations, (a) by providing data on the relative contributions of altered hormone catabolism and secretion to increased plasma glucagon levels in uremia, and (b) by evaluating the effects of uremia and dialysis on the glycemic and amino acid responses to physiological increments in plasma glucagon.…”

Section: Discussionmentioning

confidence: 96%

Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon.

Sherwin¹,

Bastl²,

Finkelstein³

et al. 1976

J. Clin. Invest.

196

View full text Add to dashboard Cite

A B S T R A C T To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range.Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and postglucose glucagon levels were three-to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two-to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls.Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three-to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glu- cagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in a 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.

show abstract

Section: Discussionmentioning

confidence: 96%

Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon.

Sherwin¹,

Bastl²,

Finkelstein³

et al. 1976

J. Clin. Invest.

196

View full text Add to dashboard Cite

show abstract

“…A broad range of abnormal blood amino acid levels have been reported in uremic man (1)(2)(3)(4). Blood alanine levels have been observed to be unaltered, increased, or decreased (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…Cyclic AMP was determined in trichloroacetic acid extracts of muscle by double-antibody radioimmunoassay (21). Adenylate cyclase activities were determined in a 50-1,u final volume containing (unless otherwise specified) 3.0 mM [a-32P]ATP (2)(3)(4) IuM), 5.0 mM MgCl2, 1 mM EDTA, 1 mM [3H]cAMP ("10,000 cpm), 24 mM bis-tris-propane-HCI buffer (pH 7.5), and an ATP-regenerating system consisting of 20 mM creatine phosphate, 0.2 mg/ml creatine phosphokinase, and 0.02 mg/ml myokinase and up to 20 ,ul of homogenate of 10,000 g particles 50-75 ,ug protein). When present, epinephrine was 10 ,uM and NaF was 10 mM.…”

Section: Introductionmentioning

confidence: 99%

The Regulation of Skeletal Muscle Alanine and Glutamine Formation and Release in Experimental Chronic Uremia in the Rat

Garber¹

1978

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 ,uM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 ,uM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO2 was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two-to fourfold or more in control than in uremic muscle. Basaland fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10lM epinephrinestimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 usM), the stimulation of membrane adenylate cyclase activity was one-to twofold greater with control membranes than with uremic muscle Dr. Garber is an investigator ofthe Howard Hughes Medical Institute.

show abstract

“…compared to 23 + 9 mg/dl ( P < 0.02) lyassy and Aviram (12) found decreased plasma levels of tryptoin control animals. A 20-cm-long segment of proximal jejunum was phan in ureniic patients compared to normal individuals after oral perfused in v i~~o with Krebs-Henseleit buffers containing amino loading and suggested that intestinal transport of this amino acid acids and carbohydrates with "C-and '11-labeled tracers.…”

mentioning

confidence: 77%

“…42 as compared to 3.47 f 0. 28 nmoles/min x cm in uremia (2,12). A recent study using rats showed variable effects the controls ( P < 0.001) . Similarly, the absorption of phenylalanine of uremia on the intestinal transport of leucine (39).…”

mentioning

confidence: 83%