Altered energetic properties in skeletal muscle of men  with well-controlled insulin-dependent (type 1) diabetes

Crowther, Gregory J.; Milstein, Jerrold M.; Jubrias, Sharon A.; Kushmerick, Martin J.; Gronka, R.; Conley, Kevin E.

doi:10.1152/ajpendo.00343.2002

Cited by 74 publications

(60 citation statements)

References 47 publications

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“…However, metabolic changes associated with diabetes are tissue-specific. For example, an increase in glycolysis was reported in skeletal muscle from type 1 and type 2 patients [28,29], while a reduction was demonstrated in diabetic heart [30,33] and in streptozotocin-induced diabetic rat retinas after 3 months of disease [34]. Our results indicate that systemic metabolic changes observed in other tissues affected by diabetes also occur in the pre-retinopathic RPE.…”

Section: Resultssupporting

confidence: 53%

“…3) participate in various metabolic pathways including glycolysis (phosphoglycerate mutase and gamma-enolase), the citric acid cycle (dihydrolipoyl dehydrogenase), lipid metabolism (sterol carrier protein x) and ketolysis (succinyl CoA: 3-ketoacid-coenzyme A transferase 1). In other tissues prone to diabetic complications, such as liver, kidney and both skeletal and heart muscle, energy metabolism is one of the key areas affected [28][29][30][31][32]. However, metabolic changes associated with diabetes are tissue-specific.…”

Section: Resultsmentioning

confidence: 99%

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Human retinal pigment epithelium proteome changes in early diabetes

et al. 2008

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Aims/hypothesis Diabetic retinopathy is the most common complication of diabetes and a leading cause of blindness among working-age adults. Anatomical and functional changes occur in the retina and retinal pigment epithelium (RPE) prior to clinical symptoms of the disease. However, the molecular mechanisms responsible for these early changes, particularly in the RPE, remain unclear. To begin defining the molecular changes associated with pre-retinopathic diabetes, we conducted a comparative proteomics study of human donor RPE. Methods The RPE was dissected from diabetic human donor eyes with no clinically apparent diabetic retinopathy (n=6) and from eyes of age-matched control donors (n= 17). Soluble proteins were separated based upon their mass and charge using two-dimensional (2-D) gel electrophoresis. Protein spots were visualised with a fluorescent dye and spot densities were compared between diabetic and control gels. Proteins from spots with significant disease-related changes in density were identified using mass spectrometry.Results Analysis of 325 spots on 2-D gels identified 31 spots that were either up-or downregulated relative to those from age-matched control donors. The protein identity of 18 spots was determined by mass spectrometry. A majority of altered proteins belonged to two major functional groups, metabolism and chaperones, while other affected categories included protein degradation, synthesis and transport, oxidoreductases, cytoskeletal structure and retinoid metabolism. Conclusions/interpretation Changes identified in the RPE proteome of pre-retinopathic diabetic donor eyes compared with age-matched controls suggest specific cellular alterations that may contribute to diabetic retinopathy. Defining the pre-retinopathic changes affecting the RPE could provide important insight into the molecular events that lead to this disease.

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Human retinal pigment epithelium proteome changes in early diabetes

et al. 2008

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“…The only study (9) to examine muscle metabolism during exercise in patients with type 1 diabetes (compared with control subjects) reported lower muscle oxidative capacity and higher glycolytic flux and acidosis. No studies have directly investigated the longitudinal effects of exercise training on muscle metabolism in these patients.…”

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confidence: 99%

Sprint Training Increases Muscle Oxidative Metabolism During High-Intensity Exercise in Patients With Type 1 Diabetes

et al. 2008

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OBJECTIVE -To investigate sprint-training effects on muscle metabolism during exercise in subjects with (type 1 diabetic group) and without (control group) type 1 diabetes.RESEARCH DESIGN AND METHODS -Eight subjects with type 1 diabetes and seven control subjects, matched for age, BMI, and maximum oxygen uptake (V O 2peak ), undertook 7 weeks of sprint training. Pretraining, subjects cycled to exhaustion at 130% V O 2peak . Posttraining subjects performed an identical test. Vastus lateralis biopsies at rest and immediately after exercise were assayed for metabolites, high-energy phosphates, and enzymes. Arterialized venous blood drawn at rest and after exercise was analyzed for lactate and [H ϩ ]. Respiratory measures were obtained on separate days during identical tests and during submaximal tests before and after training.RESULTS -Pretraining, maximal resting activities of hexokinase, citrate synthase, and pyruvate dehydrogenase did not differ between groups. Muscle lactate accumulation with exercise was higher in type 1 diabetic than nondiabetic subjects and corresponded to indexes of glycemia (A1C, fasting plasma glucose); however, glycogenolytic and glycolytic rates were similar. Posttraining, at rest, hexokinase activity increased in type 1 diabetic subjects; in both groups, citrate synthase activity increased and pyruvate dehydrogenase activity decreased; during submaximal exercise, fat oxidation was higher; and during intense exercise, peak ventilation and carbon dioxide output, plasma lactate and [H ϩ ], muscle lactate, glycogenolytic and glycolytic rates, and ATP degradation were lower in both groups.CONCLUSIONS -High-intensity exercise training was well tolerated, reduced metabolic destabilization (of lactate, H ϩ , glycogenolysis/glycolysis, and ATP) during intense exercise, and enhanced muscle oxidative metabolism in young adults with type 1 diabetes. The latter may have clinically important health benefits. Diabetes Care 31:2097-2102, 2008R epeated bouts of brief, highintensity exercise are characterized not only by marked metabolic and ionic destabilization in exercising muscle but also by progressively increasing aerobic ATP generation, such that by just the third 30-s bout, 63% of ATP is generated oxidatively (1). It is therefore not entirely surprising that high-intensity (sprint) exercise training results in oxidative adaptations in muscle. These adaptations include reduced glycogenolysis and lower accumulation of muscle lactate and hydrogen ions during high-intensity matchedwork exercise (2); increased activity of oxidative enzymes such as citrate synthase (3-5), cytochrome c oxidase (6), and ␤-hydroxyacyl-CoA dehydrogenase (␤-HAD) (4); reduced ATP degradation during intense exercise (2,5,7); and increased peak oxygen consumption (V O 2peak ) (2-5,8).The only study (9) to examine muscle metabolism during exercise in patients with type 1 diabetes (compared with control subjects) reported lower muscle oxidative capacity and higher glycolytic flux and acidosis. No studies have directly investiga...

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“…However, diabetic myopathy is a major complication of diabetes and is characterized by muscle atrophy and reduced physical performance and muscle capacity (20). Skeletal muscle from diabetic patients exhibits a higher concentration of glycolytic fibers (38), and evidence of a switch towards a glycolytic phenotype (39). Indeed, the proportion of muscle type I fibers is positively correlated with insulin sensitivity (21); and decreased levels of type I fibers are associated with insulin resistance (22).…”

Section: Discussionmentioning

confidence: 99%