Letter to the Editor: “Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris”

Liepinsh, Edgars; Dambrova, Maija

doi:10.1210/jc.2018-01408

Cited by 2 publications

(2 citation statements)

References 8 publications

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“…The shift towards long-chain acylcarnitine accumulation is a result of unbalanced acylcarnitine synthesis and mitochondrial oxidation rates, which leads to accumulation of long-chain acylcarnitines in mitochondria-often referred to in the literature as incomplete FAO. 69 In this case, the highest concentrations of long-chain acylcarnitines are found in the mitochondrial inner membrane and the intermembrane space, 70 but long-chain acylcarnitines can also escape from mitochondria and inhibit the insulin signalling cascade upstream of protein kinase b (Akt) phosphorylation, 71,72 favouring FA metabolism at the expense of glucose/pyruvate metabolism. 73 Meanwhile, in cardiac mitochondria, longchain acylcarnitines inhibit pyruvate and lactate metabolism even at physiological concentrations.…”

Section: Long-chain Acylcarnitine-induced Lipotoxicitymentioning

confidence: 99%

Altered mitochondrial metabolism in the insulin‐resistant heart

et al. 2019

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Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

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Section: Long-chain Acylcarnitine-induced Lipotoxicitymentioning

confidence: 99%

Altered mitochondrial metabolism in the insulin‐resistant heart

et al. 2019

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“…The plasma levels of FFAs and acylcarnitines increase proportionally to the duration of fasting as a result of an increase in lipolysis, and synthesis of acylcarnitines is decreased by the activation of insulin signaling during the fed or postprandial state (11). In healthy subjects, fasted-state insulin levels are low, and evaluation of FAs and acylcarnitine concentrations in a fasted state does not properly characterize insulin sensitivity (12). Instead, in the postprandial or fed state, high concentrations of free fatty acids (FFAs) and acylcarnitines are considered as markers of insulin resistance, characterizing insulin inability to stop the breakdown of triglycerides in adipocytes as well as to inhibit CPT-1-dependent FA metabolism in muscles and the heart (3,13).…”

Section: Introductionmentioning

confidence: 99%

Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity

et al. 2019

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Background: Insulin plays a pivotal role in the regulation of both carbohydrate and lipid intermediate turnover and metabolism. In the transition from a fasted to fed state, insulin action inhibits lipolysis in adipocytes, and acylcarnitine synthesis in the muscles and heart. The aim of this study was to measure free fatty acid (FFA) and acylcarnitine levels during the glucose tolerance test as indicators of tissue-specific insulin resistance. Results: Insulin release in response to glucose administration decreased both FFA and long-chain acylcarnitine levels in plasma in healthy control animals by 30% (120 min). The glucose tolerance test and [ 3 H]-deoxy-D-glucose uptake in tissues revealed that high fat diet-induced lipid overload in C57bl/6N mice evoked only adipose tissue insulin resistance, and plasma levels of FFAs did not decrease after glucose administration. In comparison, db/db mice developed type 2 diabetes with severely impaired insulin sensitivity and up to 70% lower glucose uptake in both adipose tissues and muscles (skeletal muscle and heart), and both plasma concentrations of FFAs and long-chain acylcarnitines did not decrease in response to glucose administration. Conclusions: These results link impaired adipose tissue insulin sensitivity with continuous FFA release in the transition from a fasted to postprandial state, while a blunted decrease in long-chain acylcarnitine levels is associated with muscle and heart insulin resistance.

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Letter to the Editor: “Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris”

Cited by 2 publications

References 8 publications

Altered mitochondrial metabolism in the insulin‐resistant heart

Altered mitochondrial metabolism in the insulin‐resistant heart

Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity

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