Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

Tessari, Paolo; Inchiostro, S.; Biolo, Gianni; Vincenti, E; Sabadin, L

doi:10.1172/jci115287

Cited by 76 publications

(56 citation statements)

References 32 publications

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“…The relatively lower mitochondrial content of aging muscle (32) and the decrease in mitochondrial protein synthesis that occurs with aging (16) render support to the above explanation for the discrepancy between studies performed in young and older animals. Lack of demonstrable effect of insulin on mixed muscle protein synthesis in humans is based on studies performed in mature adults (8,(11)(12)(13)(14). The differences between these human studies and studies in growing animals must therefore be cautiously interpreted, and the discrepancies could be resolved by studies based on measurements of synthesis rates of individual muscle proteins.…”

Section: Discussionmentioning

confidence: 99%

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Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

et al. 2001

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In vivo studies have reported conflicting effects of insulin on mixed tissue protein synthesis rates. To test the hypothesis that insulin has differential effects on synthesis rates of various protein fractions in different organs, we infused miniature swine (n ‫؍‬ 8 per group) with saline, insulin alone (at 0.7 mU/kg ؊1 ⅐ min ؊1 ), or insulin plus an amino acid mixture for 8 h. Fractional synthesis rate (FSR) of mitochondrial and cytoplasmic proteins in liver, heart, and skeletal muscle, as well as myosin heavy chain (MHC) in muscle, were measured using L-[1-13 C]leucine as a tracer. The FSR of mitochondrial and cytoplasmic proteins were highest in liver, followed by heart and then muscle. Mitochondrial FSR in muscle was higher during insulin and insulin plus amino acid infusions than during saline. Insulin had no significant effect on FSR of MHC in muscle. In contrast, FSR of both mitochondrial and cytoplasmic proteins were not stimulated by insulin in liver. Insulin also did not increase FSR of mitochondrial in heart, whereas insulin and amino acid stimulated FSR of cytoplasmic protein. In conclusion, insulin stimulates the synthesis of muscle mitochondrial proteins, with no significant stimulatory effect on synthesis of sarcoplasmic and MHC. These results demonstrate that insulin has different effects on synthesis rates of specific protein fractions in the liver, heart, and skeletal muscle. Diabetes

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Section: Discussionmentioning

confidence: 99%

“…Almost all human studies, with one exception (11), have reported that insulin infusion given either systemically (8,12,13) or regionally (14) does not stimulate muscle protein synthesis. Supraphysiological insulin administration, however, has been shown to stimulate muscle protein synthesis based on an arteriovenous model (15).…”

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confidence: 99%

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

et al. 2001

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“…The mode of insulin infusion appears to be a major factor in determining whether or not muscle protein synthesis will be stimulated. For example, systemic insulin infusions decrease blood amino acid concentrations (10,11,24,27,35) unless amino acids are replaced by an exogenous infusion (15,17,24,25,27). On the other hand, local insulin infusion into the leg exposes the muscle tissue to relatively high insulin levels while avoiding a major reduction in blood amino acid concentrations (2, 23).…”

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confidence: 99%

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

Bell

Fujita

Volpi

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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. Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases. Am J Physiol Endocrinol Metab 289: E999-E1006, 2005. First published July 19, 2005; doi:10.1152/ajpendo.00170.2005.-Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n ϭ 6, 162 Ϯ 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n ϭ 6, 35 Ϯ 3 kcal/h, P Ͻ 0.05 vs. HE) euglycemic hyperinsulinemic clamp with local insulin infusion in the femoral artery. Basal blood phenylalanine concentrations and phenylalanine net balance, muscle protein breakdown, and synthesis (nmol ⅐ min Ϫ1 ⅐ 100 g leg muscle Ϫ1 ) were not different between groups. During insulin infusion, femoral insulinemia increased to a similar extent between groups and blood phenylalanine concentration decreased 27 Ϯ 3% in the HE group but only 9 Ϯ 2% in the LE group (P Ͻ 0.01 HE vs. LE). Phenylalanine net balance increased in both groups, but the change was greater (P Ͻ 0.05) in the LE group. Muscle protein breakdown decreased in the HE group (58 Ϯ 12 to 35 Ϯ 7 nmol ⅐ min Ϫ1 ⅐ 100 g leg muscle Ϫ1 ) and did not change in the LE group. Muscle protein synthesis was unchanged in the HE group (39 Ϯ 6 to 30 Ϯ 7 nmol ⅐ min Ϫ1 ⅐ 100 g leg muscle Ϫ1 ) and increased (P Ͻ 0.05) in the LE group (41 Ϯ 9 to 114 Ϯ 26 nmol ⅐ min Ϫ1 ⅐ 100 g leg muscle Ϫ1 ). We conclude that amino acid availability is an important factor in the regulation of muscle protein synthesis in response to insulin, as decreased blood amino acid concentrations override the positive effect of insulin on muscle protein synthesis even if excess energy is provided.MUSCLE PROTEIN SYNTHESIS requires energy and amino acids to proceed (1, 40) and can be stimulated by insulin under certain circumstances (2). Insulin is a potent stimulus for muscle protein anabolism; however, the mechanisms by which insulin enhances muscle protein anabolism are still debated. A stimulatory effect of insulin on protein synthesis has been demonstrated in various tissues, including skeletal muscle (13,29). Moreover, in vitro and animal studies, along with recent work in humans (22), have shown that insulin can acutely stimulate muscle protein synthesis by increasing the initiation of mRNA translation (20,21,28).Previous investigations have definitively shown that amino acids provided orally (31, 36) or intravenously (1, 4, 32) stimulate human muscle protein synthesis due to the increase in blood amino acid concentrations. In addition, the amount of energy provided by the meal may also affect muscle protein synthesis (8,...

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“…insulin administration is followed by a dosedependent reduction in circulating plasma amino acid levels, with the branched chain amino acids being most sensitive to the increase in circulating insulin levels (59). This insulin-induced hypoaminoacidemia is a reflection of increased amino acid uptake from the plasma in combination with the proposed inhibitory action of increasing insulin levels on endogenous proteolysis (50,60). It has been suggested that the proposed positive effect of exogenous insulin administration on muscle protein synthesis is mediated by insulin-induced increase in blood flow and subsequent greater amino acid delivery to the muscle.…”

Section: Discussionmentioning

confidence: 98%

“…In model 1, study arms were excluded in which the insulin administration was combined with amino acid co-interventions that raised plasma amino acid above basal levels and did not have a comparator group to correct for the increase in plasma amino acids Model 2 additionally excluded study arms in which amino acid levels were allowed to drop below basal levels (41,49,50,51,52,53,54,55). This criterion excluded an additional ten study arms compared with model 1, none of which reported an effect on muscle protein synthesis.…”

Section: Data Synthesismentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

Trommelen

Groen

Hamer

et al. 2015

European Journal of Endocrinology

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Background: Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. Objective: To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. Design: A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. Conclusions: From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.

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Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

Cited by 76 publications

References 32 publications

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

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