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

Boirie‌, Yves; Short, Kevin R.; Ahlman, B.; Charlton, Michael; Nair, K. Sreekumaran

doi:10.2337/diabetes.50.12.2652

Cited by 126 publications

(80 citation statements)

References 60 publications

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“…Previous studies have meticulously revealed many of the subcellular mechanisms by which insulin stimulates muscle protein synthesis, most involving the up-regulation of translational steps (39,40). However, Boirie et al (11) showed that this up-regulation may not be a global effect on all proteins, but that specific protein pools (i.e., mitochondrial proteins) may be targeted. It may be that specific proteins having greater numbers of mRNA Insulin concentrations sustained during 7 h of insulin infusion (mean Ϯ SD).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the ratio between oxidative and glycolytic enzyme activities is decreased in skeletal muscle from type 2 diabetic subjects compared with nondiabetic subjects (6). A recent report by Boirie et al (11) on miniature swine has also demonstrated that insulin infusion preferentially stimulates the fractional synthesis rate (FSR) of skeletal muscle mitochondrial proteins. In contrast, 2 wk of insulin treatment did not stimulate muscle mitochondrial protein synthesis and cytochrome c oxidase (COX) activity in people with type 2 diabetes mellitus (DM) (12).…”

mentioning

confidence: 95%

“…At 0400 hours of each inpatient period, a priming dose of L-[1,2-13 C]leucine (1.8 mg͞kg of FFM) was administered through a peripheral forearm vein. This was followed by a continuous infusion of L- [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]leucine (1.8 mg͞kg of FFM per h). Insulin [1.5 milliunits (mU)͞kg of FFM per min] or normal saline infusion was randomized and began at 0700 hours.…”

Section: Methodsmentioning

confidence: 99%

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Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

Stump

Short

Bigelow

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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419

369

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Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P < 0.01) i.v. infused with insulin (1.5 milliunits͞kg of fat-free mass per min) while clamping glucose, amino acids, glucagon, and growth hormone. Increased ATP production occurred in association with increased mRNA levels from both mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase (COX) subunit IV] genes (164 -180%) encoding mitochondrial proteins (P < 0.05). In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05). Further studies demonstrated no effect of low to high insulin levels on muscle mitochondrial ATP production for people with type 2 diabetes mellitus, whereas matched nondiabetic controls increased 16 -26% (P < 0.02) when four different substrate combinations were used. In conclusion, insulin stimulates mitochondrial oxidative phosphorylation in skeletal muscle along with synthesis of gene transcripts and mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic patients has a reduced capacity to increase ATP production with high insulin levels.cytochrome c oxidase ͉ NADH dehydrogenase subunit IV ͉ amino acids ͉ citrate synthase

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

Stump

Short

Bigelow

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

419

369

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“…A reduced mitochondrial protein synthesis rate (as occurs in aging) (26) may contribute to muscle weakness and decrease in VO 2max . Insulin has been shown to stimulate muscle mitochondrial protein synthesis in a swine model (27). In this study, we also investigated whether muscle mitochondrial, sarcoplasmic, and mixed muscle protein synthesis are altered in people with type 2 diabetes.…”

mentioning

confidence: 99%

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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“…L'insulina è anche il maggiore regolatore delle proteine muscolari e può stimolare la sintesi delle proteine mitocondriali [63], e un danno della funzione mitocondriale può promuovere IR negli uomini [64]. L'IR è associata a un range di fattori di rischio cardiovascolare che include dislipidemia, ipertensione, intolleranza al glucosio e diabete [65].…”

Section: Danno Cardiopolmonare Nella Pcosunclassified

The polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women

Orio

Cascella

Giallauria

et al. 2016

Monaldi Arch Chest Dis

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RASSEGNA IntroduzioneLa sindrome dell'ovaio policistico (PCOS) è una tra le più comuni patologie endocrine delle donne, essendone affetto il 5-10% delle donne in età riproduttiva [1,2].La PCOS è diagnosticata in presenza di due tra i tre criteri seguenti: 1. ovaie policistiche all'ecografia pelvica 2. oligo-anovulazione 3. evidenza clinica o biochimica di iperandrogenismo (Rottherdam ESHRE-ASRM 2003) [3]. La PCOS non è solo una delle cause principali di infertilità nelle donne, ma è considerata anche una vera e propria sindrome plurimetabolica [2,4,5]: obesità [6], insulino-resistenza [7], dislipidemia [8], alterazione del sistema fibrinolitico [9], sono le conseguenze metaboliche spesso evidenti in questa sindrome.Inoltre, la PCOS è associata a rischi per la salute a lungo termine, inclusi il diabete mellito [10] e la CDV (Malattia Cardiovascolare) [11][12][13][14][15].In particolare l'insulino-resistenza, l'iperandrogenismo e la dislipidemia sono probabilmente tra i maggiori fattori di rischio per l'incidenza della CDV nella PCOS. Tali fattori di rischio cardiovascolare sono spesso evidenti in giovane età, suggerendo che le donne con PCOS, rappresentano un numeroso gruppo di donne in cui è aumentato il rischio di sviluppo precoce di CDV, anche se ciò non è attualmente dimostrato [16].È stato riportato che il rischio di malattia coronarica e di infarto del miocardio è aumentato in pazienti con PCOS rispetto a donne con cicli regolari [11], anche se la mortalità dovuta a malattia circolatoria non sembra essere incrementata [17].Recenti studi hanno dimostrato un incremento della prevalenza di CDV in donne con PCOS [14][15][16][17]. Infatti nella PCOS è stata dimostrata disfunzione endoteliale [18) e diastolica [19] ed è stata associata sia ad elevati livelli di androgeni che ad insulino-resistenza.Di recente, insieme ai classici fattori di rischio CV, come i livelli di colesterolo totale e i livelli di lipoproteine ad alta densità per il colesterolo (HDL-C), l'obesità, l'omocisteina e l'ipertrofia ventricolare sinistra si sono dimostrati essere associati, indipendentemente, ad un incremento del rischio CV [20].

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

Cited by 126 publications

References 60 publications

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

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

The polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women

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