Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Lim, Victoria S.; Yarasheski, Kevin E.; Crowley, Jan R.; Fangman, Jerry; Flanigan, Michael J.

doi:10.1097/01.asn.0000085590.83005.a0

Cited by 27 publications

(25 citation statements)

References 24 publications

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“…They found that feeding during dialysis resulted in reduced proteolysis, increased protein synthesis, and a change in net protein balance from negative to positive values. It is important to note here that insulin secretion after meal ingestion and insulin-induced protein anabolism both are intact in the ESRD patients (29,30).…”

Section: Hd Is Protein-catabolic: a Discussionmentioning

confidence: 98%

Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Lim¹,

İkizler²,

Raj³

et al. 2005

Journal of the American Society of Nephrology

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Hemodialysis (HD) is a protein catabolic procedure. Whole-body amino acid turnover studies identify dialysate amino acid loss and reduced protein synthesis as the catabolic events; proteolysis is not increased. Regional amino acid kinetics, however, document enhanced muscle protein breakdown as the cause of the catabolism; muscle protein synthesis also increased but to a lesser magnitude than the increment in protein breakdown. This discordance between whole-body and regional kinetics is best explained by the contrasting physiology between the muscle and the liver. During HD, muscle releases amino acids, which then are taken up by the liver for de novo protein synthesis. There seems to be a somatic to visceral recycling of amino acids. Evidence supporting this concept includes the increased fractional synthesis of albumin and fibrinogen during HD. It should be emphasized that region-or organ-specific kinetics vary, and whole-body turnover is a composite of all of the visceral and somatic compartments taken together. Reduced whole-body protein synthesis may be a compensatory adaptation to dialysate amino acid loss with a consequent reduction in plasma amino acid concentration. Notwithstanding the protein catabolic nature of HD, evidence is accumulating that intradialytic nutritional supplementation may blunt its catabolic effect. U ntil recently, uremia was believed to be a protein catabolic state. This view is no longer tenable because numerous whole-body amino acid turnover studies have unequivocally revealed that there is no excess protein catabolism in the chronic renal failure population in the absence of acidosis and/or concomitant illnesses (1). Uremic patients respond to low-protein diets with appropriate downregulation of whole-body proteolysis (2,3). Peritoneal dialysis is protein catabolic primarily because of protein and amino acid losses through the peritoneal effluent (4). The remaining unsettled issue is whether hemodialysis (HD) induces protein catabolism and, if it does, by what mechanism. There are theoretical reasons to believe that HD can augment protein catabolism. These include amino acid loss to the dialysate and cytokinemediated proteolysis as a result of exposure to bio-incompatible membrane and endotoxin-contaminated dialysate, but to date, investigation of protein metabolism using different techniques has yielded conflicting results. J Am Soc Nephrol Protein Metabolism during HD: A Review of the LiteratureThis article reviews the available literature of protein metabolism during HD and proposes a unifying hypothesis to explain the discordant results and diverging conclusions. The work cited in this review is categorized according to the technique used. Nitrogen Balance Combined with Urea KineticsThe seminal findings of Borah et al. (5) that nitrogen balance is always more negative or less positive, depending on the intake, on dialysis days compared with nondialysis days greatly influenced the belief that HD is a protein catabolic procedure. Lim et al. (6) also reported that nitrogen ou...

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Section: Hd Is Protein-catabolic: a Discussionmentioning

confidence: 98%

Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Lim¹,

İkizler²,

Raj³

et al. 2005

Journal of the American Society of Nephrology

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“…Fasting resulted in insulin suppression, which should stimulate eating. More importantly, feeding led to a remarkable increase in insulin secretion, the latter making anabolism possible (19).…”

Section: Discussionmentioning

confidence: 99%

Hormonal responses to fasting and refeeding in chronic renal failure patients

Deshmukh¹,

Phillips²,

O'Dorisio³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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To study anorexia in chronic renal failure (CRF) patients, we measured appetite-related hormones in seven CRF patients and four controls. Plasma concentrations and fractional changes from baseline (values from day 1, 0800) are listed as control vs. CRF (means Ϯ SE). Leptin, although higher in CRF (5.6 Ϯ 1.7 and 34 Ϯ 17 ng/ml), was suppressed after fasting; decrements were Ϫ51 Ϯ 9 and Ϫ55 Ϯ 8%. Nocturnal surge present during feeding was abolished upon fasting in both groups. Neuropeptide Y (NPY) was elevated in CRF (72 Ϯ 12 vs. 304 Ϯ 28 pg/ml, P ϭ 0.0002). NPY rhythm, reciprocal to that of leptin, was muted in CRF. Basal cortisol was similar in both groups (17 Ϯ 3 and 17 Ϯ 2 g/dl). In the controls, cortisol peaked in the morning and declined in the evening. CRF showed blunted cortisol suppression. Decrements were Ϫ61 Ϯ 3 and Ϫ20 Ϯ 9% at 1800 on day 1 (P ϭ 0.008) and Ϫ61 Ϯ 8 and Ϫ26 Ϯ 8% at 2000 on day 2 (P ϭ 0.02). Basal ACTH (25 Ϯ 5 and 54 Ϯ 16 pg/ml) as well as diurnal pattern was not statistically different between the groups. Baseline insulin was 6 Ϯ 1 and 20 Ϯ 9 U/ml. During fasting, insulin was suppressed to Ϫ64 Ϯ 10 and Ϫ51 Ϯ 9%, respectively. Upon refeeding, increments were 277 Ϯ 96 and 397 Ϯ 75%. Thus, in our CRF patients, anorexia was not due to excess leptin or deficient NPY. Impaired cortisol suppression should favor eating. Insulin suppression during fasting and secretion after feeding should enhance both eating and anabolism. The constant high NPY suggests increased tonic hypersecretion.hormones; appetite; uremia MALNUTRITION IS PREVALENT in chronic renal failure (CRF) patients, and anorexia is likely an important contributing factor (3). It has been reported that food consumption declines as renal function deteriorates (14). When uremia becomes severe, anorexia is believed to be prevalent and is characterized by food aversion, early satiety, and, sometimes, nausea and vomiting. Despite the prevalence of these symptoms, their pathogenesis has never been explained. We hypothesized that uremia-related anorexia may result from hypothalamic dysfunction. Renal failure patients are known to have a number of hormonal abnormalities due to hypothalamic disturbances; examples include diminished pulsatile gonadotropin and growth hormone secretion, lack of positive feedback effect of estrogen on LH secretion, excessive prolactin production, and delayed puberty (18). Because eating is, by and large, a central nervous system-regulated event (11), we studied some of the appetite-related hormones in response to fasting and refeeding in CRF patients. The results were compared with those obtained from normal subjects. We wondered whether CRF patients may have too much leptin or perhaps their leptin is not suppressed with food deprivation. We considered that these patients might be deficient in neuropeptide Y (NPY), a potent orexigenic peptide that mediates the effect of leptin in the hypothalamus (11). Knowing that cortisol is essential for eating in mammals and that corticotropin-releasing hormone is a potent anorex...

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“…Amino acid utilization for protein synthesis is impaired in patients with chronic renal failure (11). Anabolic response to amino acid infusion, however, was restored by concomitant administration of insulin (10,32), possibly through augmentation of intracellular amino acid transport (3).…”

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confidence: 99%

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

Raj

Adeniyi²,

Dominic³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

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Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Cited by 27 publications

References 24 publications

Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Hormonal responses to fasting and refeeding in chronic renal failure patients

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

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