Enzyme activities in quadriceps femoris muscle of obese diabetic male patients

Vondra, K; Rath, R; Bass, A; Slabochová, Z; Teisinger, Jan; Vítek, V.

doi:10.1007/bf01234508

Cited by 41 publications

(36 citation statements)

References 14 publications

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“…The role of skeletal muscle mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes has received considerable attention recently. The evidence suggests that reduced expression and activity of enzymes involved in mitochondrial processes, including oxidative phosphorylation, the tricarboxylic acid cycle and betaoxidation of fatty acids, are characteristic of insulin-resistant skeletal muscle [3][4][5][6][7][8][9]. These studies support findings that overall reductions in oxidative and phosphorylation capacity of mitochondria occur in insulin resistance and as part of the ageing process [10][11][12][13][14][15].…”

Section: Introductionsupporting

confidence: 77%

“…Given the likely role of PSARL in maintaining mitochondrial membrane integrity and function, and the known defects of mitochondria in diabetes [3,4,7,10,11,13], we suggest that altered activity of PSARL in skeletal muscle may be an important contributing factor in the development of insulin resistance and type 2 diabetes. Furthermore, the PSARL gene is located on chromosome 3q27, in a region that has been linked to obesity and type 2 diabetes in numerous genome-wide linkage scans.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated defects in oxidative pathways in skeletal muscle of subjects with obesity and/or type 2 diabetes [3,4,7,10,11,13], and it has been proposed that impaired bioenergetic capacity of skeletal muscle mitochondria is a key factor in the development of these diseases [7]. Furthermore, reduced mitochondrial function is a hallmark of the ageing process [14,15], and could be a determining factor in the development of insulin resistance and other disorders related with ageing, e.g.…”

Section: Discussionmentioning

confidence: 99%

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The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

et al. 2005

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Aims/hypothesis: This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes. Methods: We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions. Results: We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic-euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, acounting for 5% of the variation in plasma insulin in elderly subjects. Conclusions/interpretation: Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

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Section: Introductionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

et al. 2005

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“…Previous studies have shown that muscle citrate synthase is lower in type 2 diabetic people than in lean (57) and obese nondiabetic control subjects (58). In contrast, another study found no differences in muscle oxidative enzyme activity among overweight type 2 diabetic people and nondiabetic control groups (23,24,59).…”

Section: Discussionmentioning

confidence: 65%

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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“…Several pioneering trials from 1970-s reported smaller or dysfunctional mitochondria in the liver, muscle, or adipose tissue from obese and diabetic patients (Marubbio et al 1976;Petersen 1977;Vondra et al 1977), implying insufficient energy production (or excessive utilization) in different cardiometabolic disorders. Recent clinical studies confirmed above supposition using non-invasive 31 P MRS techniques to quantify ATP concentrations or synthesis in target tissues.…”

Section: Cardiometabolic Diseases and Impaired Bioenergeticsmentioning

confidence: 99%

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

Ostojić

2017

Tohoku J. Exp. Med.

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Mitochondrial energy deficit is considered a key element of different clinical pathologies -from inherited disorders of energy metabolism to drug-induced mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases. However, clinical manifestations of impaired bioenergetics are not easy to recognize, with patient-reported features usually include non-pathognomonic fatigue and weakness, or exercise intolerance, while specific lab tests are missing. Although it is not clear whether poor energetics is a primary deficit or a secondary consequence of specific disorders, improving mitochondrial viability remains a challenging task in both experimental and clinical medicine. In this review, biochemical and clinical evidence of energy deficits were reviewed, along with possible therapeutic options to tackle energy failure and restore bioenergetics.

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Enzyme activities in quadriceps femoris muscle of obese diabetic male patients

Cited by 41 publications

References 14 publications

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

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

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

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