Amino acid metabolism in uraemic patients

196

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.

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 92%

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

Sherwin¹,

Bastl²,

Finkelstein³

et al. 1976

196

“…Alterations in the plasma levels of several amino acids have been noted in patients with chronic renal failure (18)(19)(20)(21)(22)(23)(24). In this study, we examined the arterial concentrations of amino acids in both whole blood and plasma to evaluate the role of human blood cells in amino acid transport (15,16).…”

Section: Methodsmentioning

confidence: 99%

“…A wide variety of metabolic disturbances are known to ies so far available on uremic patients, only plasma concentrations of amino acids were determined (10,11,(18)(19)(20)(21)(22)(23)(24). Therefore, the potential role, if any, of the blood cell compartment in amino acid transport in such patients remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Hormone-fuel concentrations in anephric subjects. Effect of hemodialysis (with special reference to amino acids).

Ganda¹,

Aoki²,

Soeldner³

et al. 1976

A B S T R A C T Arterial blood concentrations of insulin, glucagon, and various substrates were determined in six anephric subjects in the postabsorptive state and immediately after hemodialysis. Plasma glucose and serum insulin concentrations were normal, and declined during dialysis. Plasma glucagon was elevated and remained unchanged. There was moderate hypertriglyceridemia before dialysis, but this decreased significantly after administration of heparin just before the start of dialysis, and at the end of dialysis was lowered further into the normal range.Comparison of postabsorptive whole blood concentrations of amino acids with those in normal, healthy adults revealed striking differences. Glutamine, proline, citrulline, glycine and both 1-and 3-methyl-histidines were increased, while serine, glutamate, tyrosine, lysine, and branched-chain amino acids were decreased. The glycine/serine ratio was elevated to 300% and tyrosine/ phenylalanine ratio was lowered to 60% of normal.To investigate the potential role of blood cells in amino acid transport, the distribution of individual amino acids in plasma and blood cell compartments was studied. Despite a markedly diminished blood cell mass (mean hematocrit, 20.6+1.4%), there was no significant decrease in the fraction of most amino acids present in the cell compartment, and this was explained by increases of several amino acids in cellular water. None were decreased. Furthermore, during dialysis, whole blood and plasma amino acids declined by approximately 30% and 40%, respectively, whereas no sig-

“…Amino acids such as glutamate, serine, and the branched-chain amino acids appeared to be increased 30-50% in anephric patients, compared to normal volunteers (12)(13)(14)(15), whereas other amino acids such as glutamine, citrulline, glycine, and the methyl histidines were substantially increased in uremic subjects (12)(13)(14)(15)(16). Although blood levels of other amino acids such as aspartate, threonine, histidine, and particularly alanine were found to be unchanged, plasma levels of alanine, aspartate, and threonine were increased in anephric subjects (12)(13)(14)(15)(16). Recently we observed a patient with chronic uremia and episodes of spontaneous hypoglycemia in whom hypoalaninemia and decreased rates of gluconeogenesis from alanine were found to account, at least in part, for the pathogenesis of the hypoglycemia (17).…”

Section: Introductionmentioning

confidence: 95%

Skeletal Muscle Protein and Amino Acid Metabolism in Experimental Chronic Uremia in the Rat

Garber¹

1978