Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men.

Fukagawa, Naomi K.; Minaker, Kenneth L.; Rowe, John W.; Goodman, M. N.; Matthews, Dwight E.; Bier, Dennis M.; Young, Vernon R.

doi:10.1172/jci112240

Cited by 356 publications

(139 citation statements)

References 39 publications

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“…This previous study represented acute effects of insulin and may be more comparable to the studies performed in nondiabetic individuals (31,49,50), in which insulin was infused during a short period of time. In the current study, the diabetic patients received insulin treatment over an 11-day period, although they received an insulin intravenous infusion for several hours only.…”

Section: Discussionmentioning

confidence: 87%

“…The increased circulating insulin levels on 11 days of insulin treatment substantially reduced fasting glucose levels but had little impact on circulating amino acid concentrations and amino acid kinetics, reflecting protein turnover. Previous studies in nondiabetic people demonstrated that leucine carbon flux declined progressively in a dose-dependent manner on intravenous insulin infusion (31,49,50). However, these dose-dependent effects clearly showed that the near-maximal insulin effect was achieved when insulin was infused at a dose of 1 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 (31).…”

Section: Discussionmentioning

confidence: 96%

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Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes

et al. 2002

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Improvement of glycemic status by insulin is associated with profound changes in amino acid metabolism in type 1 diabetes. In contrast, a dissociation of insulin effect on glucose and amino acid metabolism has been reported in type 2 diabetes. Type 2 diabetic patients are reported to have reduced muscle oxidative enzymes and VO 2max . We investigated the effect of 11 days of intensive insulin treatment (T 2 D؉) on whole-body amino acid kinetics, muscle protein synthesis rates, and muscle functions in eight type 2 diabetic subjects after withdrawing all treatments for 2 weeks (T 2 D؊) and compared the results with those of weight-matched lean control subjects using stable isotopes of the amino acids. Whole-body leucine, phenylalanine and tyrosine fluxes, leucine oxidation, and plasma amino acid levels were similar in all groups, although plasma glucose levels were significantly higher in T 2 D؊. Insulin treatment reduced leucine nitrogen flux and transamination rates in subjects with type 2 diabetes. Synthesis rates of muscle mitochondrial, sarcoplasmic, and mixed muscle proteins were not affected by glycemic status or insulin treatment in subjects with type 2 diabetes. Muscle strength was also unaffected by diabetes or glycemic status. In contrast, the diabetic patients showed increased tendency for muscle fatigability. Insulin treatment also failed to stimulate muscle cytochrome C oxidase activity in the diabetic patients, although it modestly elevated citrate synthase. In conclusion, improvement of glycemic status by insulin treatment did not alter whole-body amino acid turnover in type 2 diabetic subjects, but leucine nitrogen flux, transamination rates, and plasma ketoisocaproate level were decreased. Insulin treatments in subjects with type 2 diabetes had no effect on muscle mitochondrial protein synthesis and cytochrome C oxidase, a key enzyme for ATP production.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 96%

Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes

et al. 2002

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“…In normal subjects, insulin suppresses proteolysis in a dosedependent manner (17,23). Castellino et al (9) and Tessari et al (17) found that insulin also suppresses leucine oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…Castellino et al (9) and Tessari et al (17) found that insulin also suppresses leucine oxidation. Fukagawa et al (23), on the other hand, found variable effects of insulin on leucine oxidation (23). There are few studies documenting enhanced protein synthesis, one of which is that of Castellino et al (10) in CAPD patients.…”

Section: Discussionmentioning

confidence: 99%

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Lim¹,

Yarasheski²,

Crowley³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( mol/kg/h, mean Ϯ SEM) are presented in the sequence of B-HD, HD, and N, and only P Ͻ 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 Ϯ 7, 126 Ϯ 4, and 116 Ϯ 6, respectively. C (leucine oxidation rates) were 18 Ϯ 2, 17 Ϯ 2, and 21 Ϯ 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 Ϯ 6, 107 Ϯ 4, and 94 Ϯ 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were Ϫ18 Ϯ 2, Ϫ17 Ϯ 2, and Ϫ21 Ϯ 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 Ϯ 3, 98 Ϯ 6, and 94 Ϯ 5, respectively; C were 12 Ϯ 1, 11 Ϯ 2, and 18 Ϯ 1, respectively (P ϭ 0.02); S were 77 Ϯ 4, 87 Ϯ 5, and 76 Ϯ 5, respectively, and balances were Ϫ12 Ϯ 1, Ϫ11 Ϯ 2, and Ϫ18 Ϯ 1, respectively (P ϭ 0.02). During Flux 3 (high-dose insulin infusion): D were 77 Ϯ 3, 82 Ϯ 7, and 84 Ϯ 5, respectively; C were 9 Ϯ 1, 8 Ϯ 1, and 14 Ϯ 1, respectively (P ϭ 0.005); S were 68 Ϯ 4, 74 Ϯ 6, and 70 Ϯ 5, respectively, and balances were Ϫ9 Ϯ 1, Ϫ8 Ϯ 1, and Ϫ14 Ϯ 1, respectively (P ϭ 0.005). In Flux 4 (insulin infused with amino acids): D were 73 Ϯ 3, 107 Ϯ 18, and 85 Ϯ 7, respectively; C were 35 Ϯ 4, 29 Ϯ 5, and 39 Ϯ 3, respectively; S were 105 Ϯ 5, 145 Ϯ 15, and 113 Ϯ 6, respectively (P ϭ 0.02), and balances were 32 Ϯ 4, 38 Ϯ 5, and 27 Ϯ 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone reduced proteolysis and leucine oxidation, and insulin given with amino acids increased net protein synthesis.There is a prevailing view in the nephrology community that uremia is an insulin-resistant state. In reviews relating malnutrition to chronic renal failure (CRF), insulin resistance is invariably mentioned as a potential cause for the increase in protein catabolism (1-3). This perception is derived partially from the well-described phenomenon of impaired non-oxidative glucose disposal in uremic patients (4,5) and partially from findings of increased release and impaired incorporation of amino acids from and into tissue during insulin treatment in acute and chronic uremic rat models (6,7). Despite this general belief, there are few papers addressing insulin action on protein metabolism in CRF patients (8 -13). Whether uremia imparts insulin resistance and whether maintenance hemodialysis alters insulin sensitivity with regard to protein metabolism in humans is uncertain. Malnutrition is a pervasive problem in CRF patients (14 -16); it is therefore important to investigate whether insulin retains its anabolic function in this population.In ...

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“…[8][9][10]20,21 In the pediatric population, one previous study measured the effects of insulin on protein metabolism in a cohort of 4 extremely low-birth-weight neonates. 22 The investigators showed a 20% reduction in protein breakdown, although this was associated with a corresponding decrease in protein synthetic rate.…”

Section: Discussionmentioning

confidence: 99%

Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation

Agus

Javid

Ryan

et al. 2004

Journal of Pediatric Surgery

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Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men.

Cited by 356 publications

References 39 publications

Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes

Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation

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