Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers
Impaired glucose homeostasis is one of the risk factors for causing metabolic diseases including obesity, type 2 diabetes, and cancers. In glucose metabolism, pyruvate dehydrogenase complex (PDC) mediates a major regulatory step, an irreversible reaction of oxidative decarboxylation of pyruvate to a...
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| Published in | Diabetes & metabolism journal Vol. 39; no. 3; pp. 188 - 197 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
Korea (South)
Korean Diabetes Association
01.06.2015
대한당뇨병학회 |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Impaired glucose homeostasis is one of the risk factors for causing metabolic diseases including obesity, type 2 diabetes, and cancers. In glucose metabolism, pyruvate dehydrogenase complex (PDC) mediates a major regulatory step, an irreversible reaction of oxidative decarboxylation of pyruvate to acetyl-CoA. Tight control of PDC is critical because it plays a key role in glucose disposal. PDC activity is tightly regulated using phosphorylation by pyruvate dehydrogenase kinases (PDK1 to 4) and pyruvate dehydrogenase phosphatases (PDP1 and 2). PDKs and PDPs exhibit unique tissue expression patterns, kinetic properties, and sensitivities to regulatory molecules. During the last decades, the up-regulation of PDKs has been observed in the tissues of patients and mammals with metabolic diseases, which suggests that the inhibition of these kinases may have beneficial effects for treating metabolic diseases. This review summarizes the recent advances in the role of specific PDK isoenzymes on the induction of metabolic diseases and describes the effects of PDK inhibition on the prevention of metabolic diseases using pharmacological inhibitors. Based on these reports, PDK isoenzymes are strong therapeutic targets for preventing and treating metabolic diseases. |
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| AbstractList | Impaired glucose homeostasis is one of the risk factors for causing metabolic diseases including obesity, type 2 diabetes, and cancers. In glucose metabolism, pyruvate dehydrogenase complex (PDC) mediates a major regulatory step, an irreversible reaction of oxidative decarboxylation of pyruvate to acetyl-CoA. Tight control of PDC is critical because it plays a key role in glucose disposal. PDC activity is tightly regulated using phosphorylation by pyruvate dehydrogenase kinases (PDK1 to 4) and pyruvate dehydrogenase phosphatases (PDP1 and 2). PDKs and PDPs exhibit unique tissue expression patterns, kinetic properties, and sensitivities to regulatory molecules. During the last decades, the up-regulation of PDKs has been observed in the tissues of patients and mammals with metabolic diseases, which suggests that the inhibition of these kinases may have beneficial effects for treating metabolic diseases. This review summarizes the recent advances in the role of specific PDK isoenzymes on the induction of metabolic diseases and describes the effects of PDK inhibition on the prevention of metabolic diseases using pharmacological inhibitors. Based on these reports, PDK isoenzymes are strong therapeutic targets for preventing and treating metabolic diseases. Impaired glucose homeostasis is one of the risk factors for causing metabolic diseases including obesity, type 2 diabetes, and cancers. In glucose metabolism, pyruvate dehydrogenase complex (PDC) mediates a major regulatory step, an irreversible reaction of oxidative decarboxylation of pyruvate to acetyl-CoA. Tight control of PDC is critical because it plays a key role in glucose disposal. PDC activity is tightly regulated using phosphorylation by pyruvate dehydrogenase kinases (PDK1 to 4) and pyruvate dehydrogenase phosphatases (PDP1 and 2). PDKs and PDPs exhibit unique tissue expression patterns, kinetic properties, and sensitivities to regulatory molecules. During the last decades, the up-regulation of PDKs has been observed in the tissues of patients and mammals with metabolic diseases, which suggests that the inhibition of these kinases may have beneficial effects for treating metabolic diseases. This review summarizes the recent advances in the role of specific PDK isoenzymes on the induction of metabolic diseases and describes the effects of PDK inhibition on the prevention of metabolic diseases using pharmacological inhibitors. Based on these reports, PDK isoenzymes are strong therapeutic targets for preventing and treating metabolic diseases. KCI Citation Count: 19 |
| Author | Jeoung, Nam Ho |
| AuthorAffiliation | Department of Pharmaceutical Science and Technology, Catholic University of Daegu College of Medical Sciences, Gyeongsan, Korea |
| AuthorAffiliation_xml | – name: Department of Pharmaceutical Science and Technology, Catholic University of Daegu College of Medical Sciences, Gyeongsan, Korea |
| Author_xml | – sequence: 1 givenname: Nam Ho surname: Jeoung fullname: Jeoung, Nam Ho organization: Department of Pharmaceutical Science and Technology, Catholic University of Daegu College of Medical Sciences, Gyeongsan, Korea |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26124988$$D View this record in MEDLINE/PubMed https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001998760$$DAccess content in National Research Foundation of Korea (NRF) |
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| Keywords | Glucose metabolism Pyruvate dehydrogenase kinase inhibitor Pyruvate dehydrogenase kinase Diabetes mellitus, type 2 Pyruvate dehydrogenase complex Warberg effect |
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| Title | Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers |
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