Inability to stimulate skeletal muscle or whole body protein synthesis in Type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine

Bennet, W. M.; Connacher, A. A.; Smith, Kenneth; Jung, R. T.; Rennie, Michael J.

doi:10.1007/bf00586460

Cited by 75 publications

(51 citation statements)

References 53 publications

(74 reference statements)

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“…The current study further confirmed previous report by us (15,18) and others ( 17,(20)(21)(22)60 motes muscle protein synthesis (26)(27)(28)(29) probably by its effect at the posttranscriptional level (26,27). Recently, it has been reported that the insulin-induced stimulation of muscle protein synthesis takes place only in growing rats and not in fully grown rats (50).…”

Section: Discussionsupporting

confidence: 92%

“…It has been hypothesized that the lack of effect of insulin on protein synthesis in the postabsorptive state is due to the reduced supply of amino acids (secondary to insulin-induced inhibition of protein breakdown) in the fasted human subjects (8,10,18,24). Infusion of amino acids simultaneously with insulin has been reported to stimulate protein synthesis in some (14) but not in all studies (17,62). Additional studies are needed to resolve these contradictory results.…”

Section: Discussionmentioning

confidence: 99%

“…These studies consistently show either a significant increase (7,8,(10)(11)(12)(13)(14)(15)(16) or slight but not statistically significant increase of whole-body protein synthesis in insulin-deprived IDDM patients (9,17). Additional studies in IDDM patients (8,15,17,18) and in normal subjects (20)(21)(22) demonstrated that these changes in protein synthesis do not occur in the muscle protein. It was proposed that in the insulin-deprived state, increased flux of amino acids from protein breakdown increases protein synthesis in relatively insulin-insensitive tissues, such as gut and liver (18).…”

Section: Introductionmentioning

confidence: 91%

“…These are generally described as insulin's anticatabolic effect. Numerous investigators had sought to understand the mechanism of insulin's anticatabolic effect on protein (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). These studies are reviewed elsewhere (18).…”

Section: Introductionmentioning

confidence: 99%

“…Insulin also has been shown to reduce the rate of leucine oxidation (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), although it is unclear whether this is related to changes in leucine transamination or due to increased oxidation of ketoisocaproate (KIC), the transamination product of leucine. Unlike the inhibitory effect of insulin on protein breakdown and leucine oxidation, insulin's effect on protein synthesis in the fasted state remains controversial.…”

Section: Introductionmentioning

confidence: 99%

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Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Nair¹,

Ford²,

Ekberg³

et al. 1995

J. Clin. Invest.

228

232

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To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the wholebody, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-3C,'5N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-3C, 5N]-leucine, (13C)leucine, ("3C)ketoisocaproate, (2H5)phenylalanine, [21H4] tyrosine, (2H2)tyrosine, and '3CO2 were measured in arterial, hepatic vein, and femoral vein samples.Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination. (J. Clin. Invest. 1995. 95:2926-2937

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Nair¹,

Ford²,

Ekberg³

et al. 1995

J. Clin. Invest.

228

232

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Insulin and Protein Metabolism

Wolfe

Volpi

2001

Comprehensive Physiology

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The sections in this article are: Molecular Basis of Insulin Action on Protein Metabolism Protein Synthesis Protein Breakdown Transmembrane Amino Acid Transport Physiological Effects of Insulin at the Whole‐Body Level Effects of Insulin on Muscle Tissue Physiological Effects of Insulin on Other Tissues Liver Gut Heart Skin Effect of Insulin on Transport in vivo Insulin Resistance Diabetes Critical Illness Exercise Conclusion

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Effects of insulin on whole‐body and regional amino acid metabolism

Tessari

1994

Diabetes Metab. Rev.

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~ Effect Tissue References Protein degradation J Ribosome degradation Macromolecule degradation (lysosomal) t Protein synthesis T mRNA transcription T mRNA translation t mRNA stability t Ternary complex formation J AA oxidation and deamination t AA transport Skeletal muscle Fibroblasts Cardiac muscle Liver 1 5 2 7 Skeletal muscle Liver 16,24,33,34, 37,38,40,42,43 Skeletal muscle in fed animals 52 Hepatocytes 56,57,6042, Fibroblasts Skeletal muscle 145,146 AA = Amino acid. in vivo. A m f Physiol 262: E92SE935, 1992. Tessari P, Nissen SL, Miles JM, and Haymond MW: Inverse relationship of leucine flux and oxidation to free-fatty acid availability in vivo. J Clin Invest 77: 575-581, 1986. Beaufrere 8, Chassard D, Broussolle C, Riou JP, and Beylot M: Effect of D-P-hydroxybutyrate and long-and medium-chain triglycerides on leucine metabolism in humans. A m Physiol 262: E26bE274, 1992. Nair KS, Welle SL, Halliday D, and Campbell RG: Effect of P-hydroxybutyrate on wholebody leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest 92: 198-205, 1988. Miles JM, Nissen SL, Rizza RA, Gerich JE, and Haymond MW: Failure of infused betahydroxybutyrate to decrease proteolysis in man.

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Inability to stimulate skeletal muscle or whole body protein synthesis in Type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine

Cited by 75 publications

References 53 publications

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Insulin and Protein Metabolism

Effects of insulin on whole‐body and regional amino acid metabolism

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