ArticleAmerican journal of physiology. Endocrinology and metabolism2008
Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice.
Article in American journal of physiology. Endocrinology and metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction.Nature metabolism · 2026Article
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Biobanks in chronic disease management: A comprehensive review of strategies, challenges, and future directions.Heliyon · 2024Review
- Effects of HIIT training and HIIT combined with circuit resistance training on measures of physical fitness, miRNA expression, and metabolic risk factors in overweight/obese middle-aged women.BMC sports science, medicine & rehabilitation · 2024Article
- Article
- Consequences of reprogramming acetyl-CoA metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse liver.Scientific reports · 2023Article
- Analysis of a genetic region affecting mouse body weight.Physiological genomics · 2023Article
- The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.Diabetes & metabolism journal · 2023Review
- Alpha-ketoglutarate partially alleviates effects of high-fat high-fructose diet in mouse muscle.EXCLI journal · 2023Article
- Microarray analysis of hub genes, non-coding RNAs and pathways in lung after whole body irradiation in a mouse model.International journal of radiation biology · 2023Article
- Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Molecular and biochemical regulation of skeletal muscle metabolism.Journal of animal science · 2022Article
- Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, ameliorates type 2 diabetes via reduced gluconeogenesis.Heliyon · 2022Article
- Hyperpolarized NMR study of the impact of pyruvate dehydrogenase kinase inhibition on the pyruvate dehydrogenase and TCA flux in type 2 diabetic rat muscle.Pflugers Archiv : European journal of physiology · 2021Article
- BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate.International journal of molecular sciences · 2021Article
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- Pyruvate Dehydrogenase as a Therapeutic Target for Nonalcoholic Fatty Liver Disease.ACS pharmacology & translational science · 2021Review
- Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases.Journal of diabetes investigation · 2021Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The effect of pyruvate dehydrogenase kinase-4 (PDK4) deficiency on glucose homeostasis was studied in mice fed a high-fat diet. Expression of PDK4 was greatly increased in skeletal muscle and diaphragm but not liver and kidney of wild-type mice fed the high-fat diet. Wild-type and PDK4(-/-) mice consumed similar amounts of the diet and became equally obese. Insulin resistance developed in both groups. Nevertheless, fasting blood glucose levels were lower, glucose tolerance was slightly improved, and insulin sensitivity was slightly greater in the PDK4(-/-) mice compared with wild-type mice. When the mice were killed in the fed state, the actual activity of the pyruvate dehydrogenase complex (PDC) was higher in the skeletal muscle and diaphragm but not in the liver and kidney of PDK4(-/-) mice compared with wild-type mice. When the mice were killed after overnight fasting, the actual PDC activity was higher only in the kidney of PDK4(-/-) mice compared with wild-type mice. The concentrations of gluconeogenic substrates were lower in the blood of PDK4(-/-) mice compared with wild-type mice, consistent with reduced formation in peripheral tissues. Diaphragms isolated from PDK4(-/-) mice oxidized glucose faster and fatty acids slower than diaphragms from wild-type mice. Fatty acid oxidation inhibited glucose oxidation by diaphragms from wild-type but not PDK4(-/-) mice. NEFA, ketone bodies, and branched-chain amino acids were elevated more in PDK4(-/-) mice, consistent with slower rates of oxidation. These findings show that PDK4 deficiency lowers blood glucose and slightly improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.