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Gene Information

Gene symbol: PDK4

Gene name: pyruvate dehydrogenase kinase, isozyme 4

HGNC ID: 8812

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ACADL	1 hits
3	ACOT1	1 hits
4	ACOT11	1 hits
5	ACSS1	1 hits
6	ACTA1	1 hits
7	ACTN2	1 hits
8	ADHFE1	1 hits
9	ADIPOQ	1 hits
10	AKT1	1 hits
11	ATIC	1 hits
12	CD36	1 hits
13	CNBP	1 hits
14	CPT1A	1 hits
15	CREBBP	1 hits
16	EP300	1 hits
17	ESRRA	1 hits
18	ESRRB	1 hits
19	FABP2	1 hits
20	FABP3	1 hits
21	FOXO1	1 hits
22	FOXO3	1 hits
23	GCK	1 hits
24	GYG1	1 hits
25	HLA-A	1 hits
26	HNF4A	1 hits
27	INS	1 hits
28	INSR	1 hits
29	IRS1	1 hits
30	LPL	1 hits
31	MAPK1	1 hits
32	MAPK14	1 hits
33	MAPK8	1 hits
34	MAPK9	1 hits
35	MLYCD	1 hits
36	MTFR1	1 hits
37	MYH14	1 hits
38	MYH7	1 hits
39	NR0B2	1 hits
40	NR3C1	1 hits
41	PC	1 hits
42	PCK1	1 hits
43	PDC	1 hits
44	PDHB	1 hits
45	PDHX	1 hits
46	PDK1	1 hits
47	PDK2	1 hits
48	PDK3	1 hits
49	PHKA1	1 hits
50	PIK3CA	1 hits
51	PKM2	1 hits
52	PON1	1 hits
53	PON2	1 hits
54	PPARA	1 hits
55	PPARD	1 hits
56	PPARG	1 hits
57	PPARGC1A	1 hits
58	PPM2C	1 hits
59	PRKAA1	1 hits
60	PRKCA	1 hits
61	PRL	1 hits
62	PYGM	1 hits
63	SCD	1 hits
64	SLC2A4	1 hits
65	SLC37A4	1 hits
66	SLC7A1	1 hits
67	STAT5A	1 hits
68	TNC	1 hits
69	TRIM63	1 hits
70	UCP2	1 hits
71	UCP3	1 hits

Related Sentences

#	PMID	Sentence
1	8798399	Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
2	8798399	Different isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1alpha subunit, thus contributing to the regulation of glucose metabolism.
3	8798399	We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups.
4	8798399	Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
5	8798399	Different isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1alpha subunit, thus contributing to the regulation of glucose metabolism.
6	8798399	We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups.
7	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
8	9405294	This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart.
9	9405294	Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
10	9405294	Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls.
11	9405294	In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes.
12	9405294	The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
13	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
14	9405294	This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart.
15	9405294	Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
16	9405294	Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls.
17	9405294	In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes.
18	9405294	The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
19	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
20	9405294	This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart.
21	9405294	Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
22	9405294	Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls.
23	9405294	In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes.
24	9405294	The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
25	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
26	9405294	This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart.
27	9405294	Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
28	9405294	Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls.
29	9405294	In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes.
30	9405294	The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
31	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
32	9405294	This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart.
33	9405294	Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats.
34	9405294	Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls.
35	9405294	In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes.
36	9405294	The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
37	9787110	Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects.
38	9787110	Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity.
39	9787110	PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas both isoforms were negatively correlated with insulin-mediated glucose uptake rates.
40	9787110	Measurements of PDK2 and PDK4 mRNA during the hyperinsulinemic-euglycemic clamp and of PDK2 in cell culture indicated that both transcripts decrease in response to insulin.
41	9787110	Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects.
42	9787110	Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity.
43	9787110	PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas both isoforms were negatively correlated with insulin-mediated glucose uptake rates.
44	9787110	Measurements of PDK2 and PDK4 mRNA during the hyperinsulinemic-euglycemic clamp and of PDK2 in cell culture indicated that both transcripts decrease in response to insulin.
45	9787110	Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects.
46	9787110	Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity.
47	9787110	PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas both isoforms were negatively correlated with insulin-mediated glucose uptake rates.
48	9787110	Measurements of PDK2 and PDK4 mRNA during the hyperinsulinemic-euglycemic clamp and of PDK2 in cell culture indicated that both transcripts decrease in response to insulin.
49	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
50	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
51	10426378	Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex.
52	10426378	The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle.
53	10426378	Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria.
54	10426378	Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes.
55	10426378	These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions.
56	10426378	It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle.
57	10426378	Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
58	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
59	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
60	10426378	Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex.
61	10426378	The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle.
62	10426378	Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria.
63	10426378	Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes.
64	10426378	These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions.
65	10426378	It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle.
66	10426378	Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
67	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
68	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
69	10426378	Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex.
70	10426378	The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle.
71	10426378	Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria.
72	10426378	Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes.
73	10426378	These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions.
74	10426378	It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle.
75	10426378	Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
76	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
77	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
78	10426378	Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex.
79	10426378	The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle.
80	10426378	Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria.
81	10426378	Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes.
82	10426378	These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions.
83	10426378	It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle.
84	10426378	Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
85	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
86	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
87	10426378	Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex.
88	10426378	The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle.
89	10426378	Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria.
90	10426378	Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes.
91	10426378	These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions.
92	10426378	It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle.
93	10426378	Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.
94	10698691	Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression.
95	10698691	Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation.
96	10905486	Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.
97	10905486	In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate.
98	10905486	Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression.
99	10905486	The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate.
100	10905486	In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression.
101	10905486	The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding.
102	10905486	Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.
103	10905486	In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate.
104	10905486	Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression.
105	10905486	The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate.
106	10905486	In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression.
107	10905486	The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding.
108	10905486	Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.
109	10905486	In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate.
110	10905486	Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression.
111	10905486	The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate.
112	10905486	In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression.
113	10905486	The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding.
114	10905486	Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.
115	10905486	In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate.
116	10905486	Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression.
117	10905486	The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate.
118	10905486	In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression.
119	10905486	The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding.
120	10905486	Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.
121	10905486	In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate.
122	10905486	Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression.
123	10905486	The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate.
124	10905486	In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression.
125	10905486	The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding.
126	11181544	Comprehensive messenger ribonucleic acid profiling reveals that peroxisome proliferator-activated receptor gamma activation has coordinate effects on gene expression in multiple insulin-sensitive tissues.
127	11181544	Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, including the glitazone class of drugs, are insulin sensitizers that reduce glucose and lipid levels in patients with type 2 diabetes mellitus.
128	11181544	To more fully understand the molecular mechanisms underlying their therapeutic actions, we have characterized the effects of the potent, tyrosine-based PPAR gamma ligand GW1929 on serum glucose and lipid parameters and gene expression in Zucker diabetic fatty rats.
129	11181544	We used a comprehensive and unbiased messenger RNA profiling technique to identify genes regulated either directly or indirectly by PPAR gamma in epididymal white adipose tissue, interscapular brown adipose tissue, liver, and soleus skeletal muscle.
130	11181544	PPAR gamma activation stimulated the expression of a large number of genes involved in lipogenesis and fatty acid metabolism in both white adipose tissue and brown adipose tissue.
131	11181544	In muscle, PPAR gamma agonist treatment decreased the expression of pyruvate dehydrogenase kinase 4, which represses oxidative glucose metabolism, and also decreased the expression of genes involved in fatty acid transport and oxidation.
132	11181544	These changes suggest a molecular basis for PPAR gamma-mediated increases in glucose utilization in muscle.
133	11181544	In liver, PPAR gamma activation coordinately decreased the expression of genes involved in gluconeogenesis.
134	11181544	We conclude from these studies that the antidiabetic actions of PPAR gamma agonists are probably the consequence of 1) their effects on FFA levels, and 2), their coordinate effects on gene expression in multiple insulin-sensitive tissues.
135	11697863	Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding.
136	11697863	The pyruvate dehydrogenase complex (PDC) occupies a strategic role in renal intermediary metabolism, via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway.
137	11697863	In kidney, inactivation of PDC after prolonged starvation is mediated by up-regulation of the protein expression of two PDK isoforms, PDK2 and PDK4.
138	11697863	In wild-type mice, fasting (24 h) induced marked up-regulation of the protein expression of PDK4, together with modest up-regulation of PDK2 protein expression.
139	11697863	In striking contrast, renal protein expression of PDK4 was only marginally induced by fasting in PPAR alpha null mice.
140	11697863	The present results define a critical role for PPAR alpha in renal adaptation to fasting, and identify PDK4 as a downstream target of PPAR alpha activation in the kidney.
141	11697863	Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding.
142	11697863	The pyruvate dehydrogenase complex (PDC) occupies a strategic role in renal intermediary metabolism, via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway.
143	11697863	In kidney, inactivation of PDC after prolonged starvation is mediated by up-regulation of the protein expression of two PDK isoforms, PDK2 and PDK4.
144	11697863	In wild-type mice, fasting (24 h) induced marked up-regulation of the protein expression of PDK4, together with modest up-regulation of PDK2 protein expression.
145	11697863	In striking contrast, renal protein expression of PDK4 was only marginally induced by fasting in PPAR alpha null mice.
146	11697863	The present results define a critical role for PPAR alpha in renal adaptation to fasting, and identify PDK4 as a downstream target of PPAR alpha activation in the kidney.
147	11697863	Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding.
148	11697863	The pyruvate dehydrogenase complex (PDC) occupies a strategic role in renal intermediary metabolism, via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway.
149	11697863	In kidney, inactivation of PDC after prolonged starvation is mediated by up-regulation of the protein expression of two PDK isoforms, PDK2 and PDK4.
150	11697863	In wild-type mice, fasting (24 h) induced marked up-regulation of the protein expression of PDK4, together with modest up-regulation of PDK2 protein expression.
151	11697863	In striking contrast, renal protein expression of PDK4 was only marginally induced by fasting in PPAR alpha null mice.
152	11697863	The present results define a critical role for PPAR alpha in renal adaptation to fasting, and identify PDK4 as a downstream target of PPAR alpha activation in the kidney.
153	11697863	Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding.
154	11697863	The pyruvate dehydrogenase complex (PDC) occupies a strategic role in renal intermediary metabolism, via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway.
155	11697863	In kidney, inactivation of PDC after prolonged starvation is mediated by up-regulation of the protein expression of two PDK isoforms, PDK2 and PDK4.
156	11697863	In wild-type mice, fasting (24 h) induced marked up-regulation of the protein expression of PDK4, together with modest up-regulation of PDK2 protein expression.
157	11697863	In striking contrast, renal protein expression of PDK4 was only marginally induced by fasting in PPAR alpha null mice.
158	11697863	The present results define a critical role for PPAR alpha in renal adaptation to fasting, and identify PDK4 as a downstream target of PPAR alpha activation in the kidney.
159	11723055	Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.
160	11723055	The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism.
161	11723055	In this study, using antibodies against PDK1, PDK2, and PDK4 (no sufficiently specific antibodies are as yet available for PDK3), we identified the PDK isoform profile of the pancreatic islet and delineated the effects of starvation (48 h) on protein expression of individual PDK isoforms.
162	11723055	Rat islets were demonstrated to contain all three PDK isoforms, PDK1, PDK2, and PDK4.
163	11723055	Protein expression of PDK1 and PDK2 was suppressed in response to starvation (by 27% [P < 0.01] and 10% [NS], respectively).
164	11723055	We demonstrated that activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by the selective agonist WY14,643 for 24 h in vivo leads to specific upregulation of islet PDK4 protein expression by 1.8-fold (P < 0.01), in the absence of change in islet PDK1 and PDK2 protein expression but in conjunction with a 2.2-fold increase (P < 0.01) in islet PPAR-alpha protein expression.
165	11723055	Thus, although no changes in islet PPAR-alpha expression were observed after the starvation protocol, activation of PPAR-alpha in vivo may be a potential mechanism underlying upregulation of islet PDK4 protein expression in starvation.
166	11723055	We evaluated the effects of antecedent changes in PDK profile and/or PPAR-alpha activation induced by starvation or PPAR-alpha activation in vivo on glucose-stimulated insulin secretion (GSIS) in isolated islets.
167	11723055	PPAR-alpha activation in vivo led to increased insulin secretion at low glucose concentrations.
168	11723055	Our results are discussed in relation to the potential impact of changes in islet PDK profile on the insulin secretory response to lipid and of PPAR-alpha activation in the cause of fasting hyperinsulinemia.
169	11723055	Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.
170	11723055	The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism.
171	11723055	In this study, using antibodies against PDK1, PDK2, and PDK4 (no sufficiently specific antibodies are as yet available for PDK3), we identified the PDK isoform profile of the pancreatic islet and delineated the effects of starvation (48 h) on protein expression of individual PDK isoforms.
172	11723055	Rat islets were demonstrated to contain all three PDK isoforms, PDK1, PDK2, and PDK4.
173	11723055	Protein expression of PDK1 and PDK2 was suppressed in response to starvation (by 27% [P < 0.01] and 10% [NS], respectively).
174	11723055	We demonstrated that activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by the selective agonist WY14,643 for 24 h in vivo leads to specific upregulation of islet PDK4 protein expression by 1.8-fold (P < 0.01), in the absence of change in islet PDK1 and PDK2 protein expression but in conjunction with a 2.2-fold increase (P < 0.01) in islet PPAR-alpha protein expression.
175	11723055	Thus, although no changes in islet PPAR-alpha expression were observed after the starvation protocol, activation of PPAR-alpha in vivo may be a potential mechanism underlying upregulation of islet PDK4 protein expression in starvation.
176	11723055	We evaluated the effects of antecedent changes in PDK profile and/or PPAR-alpha activation induced by starvation or PPAR-alpha activation in vivo on glucose-stimulated insulin secretion (GSIS) in isolated islets.
177	11723055	PPAR-alpha activation in vivo led to increased insulin secretion at low glucose concentrations.
178	11723055	Our results are discussed in relation to the potential impact of changes in islet PDK profile on the insulin secretory response to lipid and of PPAR-alpha activation in the cause of fasting hyperinsulinemia.
179	11723055	Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.
180	11723055	The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism.
181	11723055	In this study, using antibodies against PDK1, PDK2, and PDK4 (no sufficiently specific antibodies are as yet available for PDK3), we identified the PDK isoform profile of the pancreatic islet and delineated the effects of starvation (48 h) on protein expression of individual PDK isoforms.
182	11723055	Rat islets were demonstrated to contain all three PDK isoforms, PDK1, PDK2, and PDK4.
183	11723055	Protein expression of PDK1 and PDK2 was suppressed in response to starvation (by 27% [P < 0.01] and 10% [NS], respectively).
184	11723055	We demonstrated that activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by the selective agonist WY14,643 for 24 h in vivo leads to specific upregulation of islet PDK4 protein expression by 1.8-fold (P < 0.01), in the absence of change in islet PDK1 and PDK2 protein expression but in conjunction with a 2.2-fold increase (P < 0.01) in islet PPAR-alpha protein expression.
185	11723055	Thus, although no changes in islet PPAR-alpha expression were observed after the starvation protocol, activation of PPAR-alpha in vivo may be a potential mechanism underlying upregulation of islet PDK4 protein expression in starvation.
186	11723055	We evaluated the effects of antecedent changes in PDK profile and/or PPAR-alpha activation induced by starvation or PPAR-alpha activation in vivo on glucose-stimulated insulin secretion (GSIS) in isolated islets.
187	11723055	PPAR-alpha activation in vivo led to increased insulin secretion at low glucose concentrations.
188	11723055	Our results are discussed in relation to the potential impact of changes in islet PDK profile on the insulin secretory response to lipid and of PPAR-alpha activation in the cause of fasting hyperinsulinemia.
189	11723055	Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.
190	11723055	The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism.
191	11723055	In this study, using antibodies against PDK1, PDK2, and PDK4 (no sufficiently specific antibodies are as yet available for PDK3), we identified the PDK isoform profile of the pancreatic islet and delineated the effects of starvation (48 h) on protein expression of individual PDK isoforms.
192	11723055	Rat islets were demonstrated to contain all three PDK isoforms, PDK1, PDK2, and PDK4.
193	11723055	Protein expression of PDK1 and PDK2 was suppressed in response to starvation (by 27% [P < 0.01] and 10% [NS], respectively).
194	11723055	We demonstrated that activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by the selective agonist WY14,643 for 24 h in vivo leads to specific upregulation of islet PDK4 protein expression by 1.8-fold (P < 0.01), in the absence of change in islet PDK1 and PDK2 protein expression but in conjunction with a 2.2-fold increase (P < 0.01) in islet PPAR-alpha protein expression.
195	11723055	Thus, although no changes in islet PPAR-alpha expression were observed after the starvation protocol, activation of PPAR-alpha in vivo may be a potential mechanism underlying upregulation of islet PDK4 protein expression in starvation.
196	11723055	We evaluated the effects of antecedent changes in PDK profile and/or PPAR-alpha activation induced by starvation or PPAR-alpha activation in vivo on glucose-stimulated insulin secretion (GSIS) in isolated islets.
197	11723055	PPAR-alpha activation in vivo led to increased insulin secretion at low glucose concentrations.
198	11723055	Our results are discussed in relation to the potential impact of changes in islet PDK profile on the insulin secretory response to lipid and of PPAR-alpha activation in the cause of fasting hyperinsulinemia.
199	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
200	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
201	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
202	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
203	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
204	11812733	Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids.
205	11812733	Insulin also decreased the abundance of the PDK2 message.
206	11812733	The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes.
207	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
208	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
209	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
210	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
211	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
212	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
213	11812733	Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids.
214	11812733	Insulin also decreased the abundance of the PDK2 message.
215	11812733	The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes.
216	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
217	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
218	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
219	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
220	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
221	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
222	11812733	Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids.
223	11812733	Insulin also decreased the abundance of the PDK2 message.
224	11812733	The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes.
225	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
226	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
227	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
228	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
229	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
230	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
231	11812733	Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids.
232	11812733	Insulin also decreased the abundance of the PDK2 message.
233	11812733	The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes.
234	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
235	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
236	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
237	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
238	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
239	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
240	11812733	Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids.
241	11812733	Insulin also decreased the abundance of the PDK2 message.
242	11812733	The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes.
243	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
244	11851361	STZ increased humoral (glucose and non-esterified fatty acids) and heart gene expression (myosin heavy chain beta, pyruvate dehydrogenase kinase 4 and uncoupling protein 3) markers of diabetes.
245	11916905	Consistent with its metabolic actions, GW7647 induced mRNA expression of mitochondrial enzymes that promote fatty acid catabolism; carnitine palmityltransferase 1 and malonyl-CoA decarboxylase increased approximately 2-fold, whereas pyruvate dehydrogenase kinase 4 increased 45-fold.
246	12023878	The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-alpha (PPARalpha) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARalpha-null mice.
247	12023878	PPARalpha deficiency also impaired hepatic glycogen repletion (P<0.001), despite normal insulin and glucose levels after refeeding.
248	12023878	This difference was reflected by corresponding changes in the relationship between plasma insulin and the mRNA expression of the lipogenic transcription factor sterol-regulatory-element-binding protein-1c, and that of one of its known targets, fatty acid synthase.
249	12023878	In wild-type mice, hepatic pyruvate dehydrogenase kinase (PDK) 4 protein expression (a downstream marker of altered fatty acid catabolism) increased (P<0.01) in response to fasting, with suppression (P<0.001) by refeeding.
250	12023878	Although PDK4 up-regulation after fasting was halved by PPARalpha deficiency, PDK4 suppression after refeeding was attenuated.
251	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
252	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
253	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
254	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
255	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
256	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
257	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
258	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
259	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
260	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
261	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
262	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
263	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
264	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
265	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
266	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
267	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
268	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
269	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
270	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
271	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
272	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
273	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
274	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
275	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
276	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
277	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
278	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
279	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
280	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
281	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
282	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
283	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
284	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
285	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
286	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
287	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
288	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
289	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
290	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
291	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
292	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
293	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
294	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
295	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
296	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
297	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
298	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
299	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
300	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
301	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
302	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
303	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
304	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
305	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
306	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
307	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
308	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
309	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
310	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
311	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
312	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
313	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
314	12049632	Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
315	12049632	Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4.
316	12049632	The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism.
317	12049632	PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.
318	12049632	PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation.
319	12049632	By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression.
320	12049632	PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice).
321	12049632	Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state.
322	12049632	Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.
323	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
324	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
325	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
326	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
327	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
328	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
329	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
330	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
331	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
332	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
333	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
334	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
335	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
336	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
337	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
338	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
339	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
340	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
341	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
342	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
343	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
344	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
345	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
346	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
347	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
348	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
349	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
350	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
351	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
352	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
353	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
354	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
355	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
356	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
357	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
358	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
359	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
360	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
361	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
362	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
363	12099888	Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).
364	12099888	In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC.
365	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
366	12099888	Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.
367	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
368	12099888	We evaluated the participation of PPARalpha in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres.
369	12099888	In the fed state, acute (24 h) activation of PPARalpha by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis.
370	12099888	Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.
371	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
372	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
373	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
374	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
375	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
376	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
377	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
378	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
379	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
380	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
381	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
382	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
383	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
384	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
385	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
386	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
387	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
388	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
389	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
390	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
391	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
392	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
393	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
394	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
395	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
396	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
397	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
398	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
399	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
400	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
401	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
402	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
403	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
404	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
405	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
406	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
407	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
408	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
409	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
410	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
411	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
412	12435272	Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
413	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
414	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
415	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
416	12435272	Administration of the selective PPAR-alpha activator WY14,643 significantly increased PDK4 protein to a similar extent in both control and high-fat-fed rats, but WY14,643 treatment and hyperthyroidism did not have additive effects on hepatic PDK4 protein expression.
417	12435272	PPARalpha activation did not influence hepatic PDK2 protein expression in euthyroid rats, suggesting that up-regulation of PDK2 by hyperthyroidism does not involve PPARalpha, but attenuated the effect of hyperthyroidism to increase hepatic PDK2 expression.
418	12435272	The results indicate that hepatic PDK4 up-regulation can be achieved by heterodimerization of either PPARalpha or TR with the RXR receptor and that effects of PPARalpha activation on hepatic PDK2 and PDK4 expression favour a switch towards preferential expression of PDK4.
419	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
420	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
421	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
422	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
423	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
424	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
425	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
426	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
427	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
428	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
429	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
430	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
431	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
432	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
433	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
434	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
435	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
436	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
437	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
438	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
439	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
440	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
441	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
442	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
443	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
444	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
445	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
446	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
447	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
448	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
449	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
450	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
451	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
452	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
453	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
454	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
455	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
456	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
457	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
458	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
459	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
460	12476789	This review describes recent advances relating to the control of mammalian PDC activity by phosphorylation (inactivation) and dephosphorylation (activation, reactivation), in particular regulation of PDC by pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates PDC.
461	12476789	PDK2 and PDK4 appear to be expressed in most major tissues and organs of the body, PDK1 appears to be limited to the heart and pancreatic islets, and PDK3 is limited to the kidney, brain and testis.
462	12476789	PDK4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance, diabetes mellitus and hyperthyroidism.
463	12476789	Parallel increases in PDK2 and PDK4 expression appear to be restricted to gluconceogenesic tissues, liver and kidney, which take up as well as generate pyruvate.
464	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
465	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
466	12476789	PPAR alpha deficiency in liver and kidney restricts starvation-induced upregulation of PDK4; however, the role of PPAR alpha in heart and skeletal muscle appears to be more complex.
467	12606505	Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes.
468	12606505	Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels.
469	12606505	However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively).
470	12606505	Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals.
471	12606505	Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes.
472	12606505	Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels.
473	12606505	However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively).
474	12606505	Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals.
475	12606505	Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes.
476	12606505	Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels.
477	12606505	However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively).
478	12606505	Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals.
479	12637257	Decreased pyruvate oxidation in IUGR mitochondria was associated with decreased ATP production, decreased pyruvate dehydrogenase activity, and increased expression of pyruvate dehydrogenase kinase 4.
480	12637257	Impaired ATP synthesis in muscle compromises energy-dependent GLUT4 recruitment to the cell surface, glucose transport, and glycogen synthesis, which contribute to insulin resistance and hyperglycemia of type 2 diabetes.
481	12642386	Conversely, we established that the regulation of the pyruvate dehydrogenase kinase (PDK4) gene in the heart, by rexinoids, is independent of PPARalpha expression. (4) Our results support the obligatory expression of the active, although quiescent, PPARalpha to sustain a subset of relevant regulations attributable to rexinoids in the liver and kidney.
482	14563825	Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone.
483	14563825	In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased.
484	14563825	The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA.
485	14563825	The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction.
486	14563825	Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity.
487	14563825	In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle.
488	14563825	Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone.
489	14563825	In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased.
490	14563825	The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA.
491	14563825	The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction.
492	14563825	Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity.
493	14563825	In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle.
494	15026305	Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.
495	15026305	Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression.
496	15026305	PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
497	15026305	In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
498	15026305	PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
499	15026305	In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
500	15026305	Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.
501	15026305	Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression.
502	15026305	PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
503	15026305	In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
504	15026305	PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
505	15026305	In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
506	15026305	Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.
507	15026305	Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression.
508	15026305	PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
509	15026305	In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
510	15026305	PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
511	15026305	In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
512	15026305	Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.
513	15026305	Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression.
514	15026305	PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
515	15026305	In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
516	15026305	PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
517	15026305	In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
518	15026305	Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA.
519	15026305	Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression.
520	15026305	PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion).
521	15026305	In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease.
522	15026305	PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion.
523	15026305	In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.
524	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
525	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
526	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
527	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
528	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
529	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
530	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
531	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
532	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
533	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
534	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
535	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
536	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
537	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
538	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
539	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
540	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
541	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
542	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
543	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
544	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
545	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
546	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
547	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
548	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
549	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
550	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
551	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
552	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
553	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
554	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
555	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
556	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
557	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
558	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
559	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
560	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
561	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
562	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
563	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
564	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
565	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
566	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
567	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
568	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
569	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
570	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
571	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
572	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
573	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
574	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
575	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
576	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
577	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
578	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
579	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
580	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
581	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
582	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
583	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
584	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
585	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
586	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
587	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
588	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
589	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
590	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
591	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
592	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
593	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
594	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
595	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
596	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
597	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
598	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
599	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
600	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
601	15047604	Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity.
602	15047604	A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter.
603	15047604	Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression.
604	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
605	15292029	In the current study, pyruvate dehydrogenase kinase 4 (pdk4) was utilized as a representative PPAR alpha-regulated gene.
606	15292029	The same pattern of induction was observed for the PPAR alpha-regulated genes malonyl-CoA decarboxylase and uncoupling protein 3.
607	15312755	Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima Fatty rat both before and after the onset of diabetes mellitus.
608	15312755	The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible oxidative decarboxylation of pyruvate in mitochondria.
609	15312755	These results suggest that concomitant greater PDK4 and less PDP1 expression in skeletal muscle of OLETF rats before the onset of diabetes are responsible for the lowering of the PDC activity and may be related with the development of diabetes mellitus.
610	15776585	[Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal].
611	15776585	We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2).
612	15776585	[Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal].
613	15776585	We reported a study about three candidate genes which may be involved in non-insulin dependent diabetes mellitus (NIDDM): Pyruvate Dehydrogenase Kinase 4 (PDK4), Paraoxonase 2 (PON2) and Fatty Acid Binding Protein 2 (FABP2).
614	15831517	Data from in vitro binding, cotransfection, and cofactor recruitment assays characterize LSN862 as a high-affinity PPARgamma partial agonist with relatively less but significant PPARalpha agonist activity.
615	15831517	Using these same assays, rosiglitazone was characterized as a high-affinity PPARgamma full agonist with no PPARalpha activity.
616	15831517	Only LSN862 significantly elevated mRNA levels of pyruvate dehydrogenase kinase isozyme 4 and bifunctional enzyme in the liver and lipoprotein lipase in both fat depots.
617	15831517	These findings show that PPARgamma full agonist activity is not necessary to achieve potent and efficacious insulin-sensitizing benefits and demonstrate the therapeutic advantages of a PPARalpha/gamma dual agonist.
618	15866483	The aim of this work was to study whether the exposure of skeletal muscle cells to palmitate affected peroxisome proliferator-activated receptor (PPAR) beta/delta activity.
619	15866483	Here, we report that exposure of C2C12 skeletal muscle cells to 0.75 mM palmitate reduced (74%, P<0.01) the mRNA levels of the PPARbeta/delta-target gene pyruvatedehydrogenase kinase 4 (PDK-4), which is involved in fatty acid utilization.
620	15866483	Increased NF-kappaB activity after palmitate exposure was associated with enhanced protein-protein interaction between PPARbeta/delta and p65.
621	15866483	These results indicate that palmitate may reduce fatty acid utilization in skeletal muscle cells by reducing PPARbeta/delta signaling through increased NF-kappaB activity.
622	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
623	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
624	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
625	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
626	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
627	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
628	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
629	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
630	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
631	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
632	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
633	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
634	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
635	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
636	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
637	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
638	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
639	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
640	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
641	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
642	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
643	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
644	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
645	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
646	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
647	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
648	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
649	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
650	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
651	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
652	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
653	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
654	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
655	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
656	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
657	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
658	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
659	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
660	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
661	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
662	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
663	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
664	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
665	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
666	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
667	15967803	Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator.
668	15967803	The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA.
669	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
670	15967803	There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased.
671	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
672	15967803	We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes.
673	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
674	15967803	Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
675	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
676	16324918	In skeletal muscle, the expression of 55 genes increased and 245 decreased involving genes related to glucose metabolism (eg, phosphorylase kinase, pyruvate dehydrogenase kinase 4), lipid metabolism (eg, carnitine palmitoyltransferase 1, fatty acid transporter), and signaling pathways (eg, mitogen-activated protein kinases, protein kinase C).
677	16483874	The activity of the pyruvate dehydrogenase complex (PDC) is regulated by covalent modification of its E1 component, which is catalyzed by specific pyruvate dehydrogenase kinases (PDKs) and phosphatases.
678	16483874	In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is scarce in the body.
679	16483874	Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages.
680	16483874	These results suggest that persistently elevated levels of circulating free fatty acid in normal and diabetic OLETF rats play an important role in stimulating PDK2 and PDK4 expression in liver.
681	16483874	The activity of the pyruvate dehydrogenase complex (PDC) is regulated by covalent modification of its E1 component, which is catalyzed by specific pyruvate dehydrogenase kinases (PDKs) and phosphatases.
682	16483874	In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is scarce in the body.
683	16483874	Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages.
684	16483874	These results suggest that persistently elevated levels of circulating free fatty acid in normal and diabetic OLETF rats play an important role in stimulating PDK2 and PDK4 expression in liver.
685	16483874	The activity of the pyruvate dehydrogenase complex (PDC) is regulated by covalent modification of its E1 component, which is catalyzed by specific pyruvate dehydrogenase kinases (PDKs) and phosphatases.
686	16483874	In the liver, PDK2 and PDK4 are the most abundant PDK isoforms, which are responsible for inactivation of PDC when glucose availability is scarce in the body.
687	16483874	Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages.
688	16483874	These results suggest that persistently elevated levels of circulating free fatty acid in normal and diabetic OLETF rats play an important role in stimulating PDK2 and PDK4 expression in liver.
689	16873695	Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.
690	16873695	We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
691	16873695	In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
692	16873695	Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05).
693	16873695	Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
694	16873695	These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
695	16873695	Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle.
696	16873695	Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.
697	16873695	We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
698	16873695	In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
699	16873695	Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05).
700	16873695	Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
701	16873695	These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
702	16873695	Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle.
703	16873695	Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.
704	16873695	We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
705	16873695	In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
706	16873695	Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05).
707	16873695	Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
708	16873695	These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
709	16873695	Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle.
710	16873695	Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.
711	16873695	We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
712	16873695	In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
713	16873695	Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05).
714	16873695	Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
715	16873695	These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
716	16873695	Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle.
717	16873695	Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states.
718	16873695	We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle.
719	16873695	In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation.
720	16873695	Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05).
721	16873695	Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions.
722	16873695	These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation.
723	16873695	Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle.
724	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
725	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
726	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
727	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
728	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
729	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
730	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
731	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
732	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
733	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
734	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
735	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
736	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
737	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
738	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
739	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
740	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
741	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
742	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
743	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
744	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
745	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
746	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
747	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
748	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
749	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
750	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
751	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
752	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
753	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
754	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
755	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
756	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
757	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
758	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
759	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
760	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
761	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
762	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
763	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
764	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
765	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
766	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
767	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
768	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
769	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
770	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
771	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
772	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
773	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
774	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
775	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
776	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
777	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
778	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
779	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
780	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
781	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
782	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
783	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
784	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
785	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
786	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
787	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
788	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
789	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
790	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
791	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
792	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
793	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
794	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
795	17079227	The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA.
796	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
797	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
798	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
799	17079227	Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism.
800	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
801	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
802	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
803	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
804	17132539	The mechanisms that control mammalian pyruvate dehydrogenase complex (PDC) activity include its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDKs 1 - 4).
805	17132539	Here we review new developments in the regulation of the activities and expression of the PDKs, in particular PDK2 and PDK4, in relation to glucose and lipid homeostasis.
806	17132539	This review describes recent advances relating to the acute and long-term modes of regulation of the PDKs, with particular emphasis on the regulatory roles of nuclear receptors including peroxisome proliferator-activated receptor (PPAR) alpha and Liver X receptor (LXR), PPAR gamma coactivator alpha (PGC-1alpha) and insulin, and the impact of changes in PDK activity and expression in glucose and lipid homeostasis.
807	17161237	Fasting serum haptoglobin, insulin, and C-peptide were assayed, and select messenger RNA (mRNA) and protein markers of inflammation and glucose metabolism were measured in adipose and liver tissues.
808	17161237	The CLA-fed fa/fa rats also had greater adipose glucose transporter-4 mRNA and less adipose tumor necrosis factor alpha mRNA and protein compared with control-fed fa/fa rats.
809	17161237	In contrast, other markers of inflammation and glucose metabolism including adipose macrophage inflammatory factor, macrophage inflammatory protein-2, and liver pyruvate carboxylase and pyruvate dehydrogenase kinase 4 were not significantly changed.
810	17310282	Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.
811	17310282	The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4).
812	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
813	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
814	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
815	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
816	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
817	17360981	PDK4 is a STAT5A target gene.
818	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
819	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
820	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
821	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
822	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
823	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
824	17360981	PDK4 is a STAT5A target gene.
825	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
826	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
827	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
828	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
829	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
830	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
831	17360981	PDK4 is a STAT5A target gene.
832	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
833	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
834	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
835	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
836	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
837	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
838	17360981	PDK4 is a STAT5A target gene.
839	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
840	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
841	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
842	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
843	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
844	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
845	17360981	PDK4 is a STAT5A target gene.
846	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
847	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
848	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
849	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
850	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
851	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
852	17360981	PDK4 is a STAT5A target gene.
853	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
854	17360981	The STAT5A-mediated induction of pyruvate dehydrogenase kinase 4 expression by prolactin or growth hormone in adipocytes.
855	17360981	The purpose of this study was to determine whether pyruvate dehydrogenase kinase (PDK)4 was expressed in adipocytes and whether PDK4 expression was hormonally regulated in fat cells.
856	17360981	Our studies demonstrate that PRL and porcine GH can induce the expression of PDK4 in 3T3-L1 adipocytes.
857	17360981	Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression.
858	17360981	In addition, we identified a hormone-responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region that mediates the PRL (sheep) and GH (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.
859	17360981	PDK4 is a STAT5A target gene.
860	17360981	PRL is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to PRL-induced insulin resistance.
861	17363743	High-density oligonucleotide arrays were used to compare gene expression of rat hearts from control, untreated diabetic, and diabetic groups treated with islet cell transplantation (ICT), protein kinase C (PKC)beta inhibitor ruboxistaurin, or ACE inhibitor captopril.
862	17363743	In cardiomyocytes, PKC inhibition attenuated fatty acid-induced increases in the metabolic genes PDK4 and UCP3 and also prevented fatty acid-mediated inhibition of basal and insulin-stimulated glucose oxidation.
863	17363743	Thus, PKCbeta or ACE inhibitors may ameliorate cardiac metabolism and function in diabetes partly by normalization of fuel metabolic gene expression directly in the myocardium.
864	17500064	Concomitant with these metabolic changes, we provide evidence that GW501516 increases the expression of key genes involved in lipid metabolism (FABP3, CPT1, and PDK4) by a PPARdelta-dependent mechanism.
865	17550347	Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet.
866	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
867	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
868	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
869	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
870	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
871	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
872	18083902	Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy.
873	18083902	To study the long-term consequences of impaired metabolic flexibility, we have generated mice that overexpress pyruvate dehydrogenase kinase (PDK)4 selectively in the heart.
874	18308721	CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress.
875	18308721	Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects.
876	18308721	In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation.
877	18308721	Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo.
878	18308721	FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA.
879	18308721	CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress.
880	18308721	Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects.
881	18308721	In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation.
882	18308721	Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo.
883	18308721	FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA.
884	18308721	CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress.
885	18308721	Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects.
886	18308721	In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation.
887	18308721	Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo.
888	18308721	FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA.
889	18308721	CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress.
890	18308721	Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects.
891	18308721	In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation.
892	18308721	Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo.
893	18308721	FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA.
894	18468620	Under various pathophysiological muscle-wasting conditions, such as diabetes and starvation, a family of ubiquitin ligases, including muscle-specific RING-finger protein 1 (MuRF1), are induced to target muscle proteins for degradation via ubiquitination.
895	18468620	Comparison of quadriceps from MuRF1-TG and wild type mice did not reveal elevated multi-ubiquitination of myosin as observed in human patients with muscle wasting.
896	18468620	Instead, MuRF1-TG mice expressed lower levels of pyruvate dehydrogenase (PDH), a mitochondrial key enzyme in charge of glycolysis, and of its regulator PDK2.
897	18468620	Furthermore, yeast two-hybrid interaction studies demonstrated the interaction of MuRF1 with PDH, PDK2, PDK4, PKM2 (all participating in glycolysis) and with phosphorylase beta (PYGM) and glycogenin (both regulating glycogen metabolism).
898	18468620	Consistent with the idea that MuRF1 may regulate carbohydrate metabolism, MuRF1-TG mice had twofold elevated insulin blood levels and lower hepatic glycogen contents.
899	18468620	Taken together, our data demonstrate that MuRF1 expression in skeletal muscle re-directs glycogen synthesis to the liver and stimulates pancreatic insulin secretion, thereby providing a regulatory feedback loop that connects skeletal muscle metabolism with the liver and the pancreas during metabolic stress.
900	18519799	Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue.
901	18658136	Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
902	18658136	Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4.
903	19264873	Muscle-specific overexpression of heparin-binding epidermal growth factor-like growth factor increases peripheral glucose disposal and insulin sensitivity.
904	19264873	In the present study, we found that exercise up-regulates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in skeletal muscle.
905	19264873	These changes were accompanied by increased kinase activity of Akt in skeletal muscle and consequent inhibition of Forkhead box O1-dependent expression of the pyruvate dehydrogenase kinase 4 gene.
906	19264873	Our results suggest that HB-EGF produced by contracting muscle acts as an insulin sensitizer that facilitates peripheral glucose disposal.
907	19503617	We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1), ACTA1 (actin, alpha 1, skeletal muscle), ACTN2 (actinin, alpha 2), ADHFE1 (alcohol dehydrogenase, iron containing, 1), MTFR1 (mitochondrial fission regulator 1), PDK4 (pyruvate dehydrogenase kinase, isozyme 4) and TNC (tenascin C).
908	20040361	The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor delta (PPARdelta) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic beta-cells.
909	20040361	GW-induced activation of PPARdelta up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells.
910	20094041	Although germ-line deletion of c-Jun NH(2)-terminal kinase (JNK) improves overall insulin sensitivity in mice, those studies could not reveal the underlying molecular mechanism and the tissue site(s) in which reduced JNK activity elicits the observed phenotype.
911	20094041	Given its importance in nonesterified fatty acids (NEFA) and glucose utilization, we hypothesized that the insulin-sensitive phenotype associated with Jnk deletion originates from loss of JNK function in skeletal muscle.
912	20094041	We show for the first time that cellular JNK2- and JNK1/JNK2-deficiency divert glucose from oxidation to glycogenesis due to increased glycogen synthase (GS) activity and induction of Pdk4.
913	20094041	We further show that JNK2- and JNK1/JNK2-deficiency profoundly increase cellular NEFA oxidation, and their conversion to phospholipids and triglyceride.
914	20094041	The increased NEFA utilization was coupled to increased expressions of selective NEFA handling genes including Cd36, Acsl4, and Chka, and enhanced palmitic acid (PA)-dependent suppression of acetyl-CoA carboxylase (Acc).
915	20094041	In JNK-intact cells, PA inhibited insulin signaling and glycogenesis.
916	20094041	Although silencing Jnk1 and/or Jnk2 prevented PA-induced inhibition of insulin signaling, it did not completely block decreased insulin-mediated glycogenesis, thus indicating JNK-independent pathways in the suppression of glycogenesis by PA.
917	20094041	Muscle-specific inhibition of JNK2 (or total JNK) improves the capacity of NEFA utilization and glycogenesis, and is a potential therapeutic target for improving systemic insulin sensitivity in type 2 diabetes (T2D).
918	20427484	Although FK506-binding protein 52 (FKBP52) is an established positive regulator of glucocorticoid receptor (GR) activity, an in vivo role for FKBP52 in glucocorticoid control of metabolism has not been reported.
919	20427484	To address this question, FKBP52(+/-) mice were placed on a high-fat (HF) diet known to induce obesity, hepatic steatosis, and insulin resistance.
920	20427484	In response to HF, FKBP52(+/-) mice demonstrated a susceptibility to hyperglycemia and hyperinsulinemia that correlated with reduced insulin clearance and reduced expression of hepatic CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a mediator of clearance.
921	20427484	Livers of HF-fed mutant mice had high lipid content and elevated expression of lipogenic genes (peroxisome proliferator-activated receptor gamma, fatty acid synthase, and sterol regulatory element-binding protein 1c) and inflammatory markers (TNFalpha).
922	20427484	Interestingly, mutant mice under HF showed elevated serum corticosterone, but their steatotic livers had reduced expression of gluconeogenic genes (phosphoenolpyruvate carboxy kinase, glucose 6 phosphatase, and pyruvate dehydrogenase kinase 4), whereas muscle and adipose expressed normal to elevated levels of glucocorticoid markers.
923	20427484	Consistent with this hypothesis, reduced expression of gluconeogenic genes and CEACAM1 was observed in dexamethasone-treated FKBP52-deficient mouse embryonic fibroblast cells.
924	20484462	Prolactin (PRL) induces beta-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production.
925	20484462	We used rat islets and insulinoma (INS-1) cells to explore the interactions of PRL, glucose, and dexamethasone (DEX) in the regulation of beta-cell pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), and the pyruvate dehydrogenase kinases (PDKs), which catalyze the phosphorylation and inactivation of PDH.
926	20484462	In INS-1 cells, PRL increased PDH activity 1.4- to 2-fold (P < 0.05-0.001) at glucose concentrations ranging from 2.5-11 mm.
927	20484462	DEX reduced PDH activity; this effect was reversed by PRL.
928	20484462	PDK1, -2, -3, and -4 mRNAs were detected in both islets and insulinoma cells, but the latter expressed trivial amounts of PDK4.
929	20484462	PRL reduced PDK2 mRNA and protein levels in rat islets and INS-1 cells and PDK4 mRNA in islets; DEX increased PDK2 mRNA in islets and INS-1 cells; this effect was reversed by PRL.
930	20484462	Our findings suggest that PRL induction of GSIS is mediated by increases in beta-cell PDH activity; this is facilitated by suppression of PDKs.
931	20484462	PRL counteracts the effects of DEX on PDH and PDK expression, suggesting novel roles for the lactogens in the defense against diabetes.
932	20484462	Prolactin (PRL) induces beta-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production.
933	20484462	We used rat islets and insulinoma (INS-1) cells to explore the interactions of PRL, glucose, and dexamethasone (DEX) in the regulation of beta-cell pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), and the pyruvate dehydrogenase kinases (PDKs), which catalyze the phosphorylation and inactivation of PDH.
934	20484462	In INS-1 cells, PRL increased PDH activity 1.4- to 2-fold (P < 0.05-0.001) at glucose concentrations ranging from 2.5-11 mm.
935	20484462	DEX reduced PDH activity; this effect was reversed by PRL.
936	20484462	PDK1, -2, -3, and -4 mRNAs were detected in both islets and insulinoma cells, but the latter expressed trivial amounts of PDK4.
937	20484462	PRL reduced PDK2 mRNA and protein levels in rat islets and INS-1 cells and PDK4 mRNA in islets; DEX increased PDK2 mRNA in islets and INS-1 cells; this effect was reversed by PRL.
938	20484462	Our findings suggest that PRL induction of GSIS is mediated by increases in beta-cell PDH activity; this is facilitated by suppression of PDKs.
939	20484462	PRL counteracts the effects of DEX on PDH and PDK expression, suggesting novel roles for the lactogens in the defense against diabetes.
940	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
941	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
942	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
943	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
944	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
945	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
946	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
947	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
948	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
949	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
950	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
951	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
952	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
953	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
954	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
955	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
956	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
957	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
958	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
959	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
960	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
961	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
962	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
963	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
964	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
965	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
966	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
967	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
968	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
969	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
970	20943752	The mRNA levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 in the liver were significantly lower in CPP-fed mice than in high-fat control mice.
971	21076574	Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels.
972	21076574	In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle.
973	21162119	Pyruvate dehydrogenase kinase 4 (PDK4) is a lipid status responsive gene involved in muscle fuel selection.
974	21162119	Factors that regulate PDK4 mRNA expression include plasma corticosterone, insulin and free fatty acids.
975	21162119	The model indicated that corticosterone had a moderate effect and PDK4 was more sensitive to free fatty acid than insulin fluxes, which was in good agreement with the literature data.
976	21162119	Pyruvate dehydrogenase kinase 4 (PDK4) is a lipid status responsive gene involved in muscle fuel selection.
977	21162119	Factors that regulate PDK4 mRNA expression include plasma corticosterone, insulin and free fatty acids.
978	21162119	The model indicated that corticosterone had a moderate effect and PDK4 was more sensitive to free fatty acid than insulin fluxes, which was in good agreement with the literature data.
979	21162119	Pyruvate dehydrogenase kinase 4 (PDK4) is a lipid status responsive gene involved in muscle fuel selection.
980	21162119	Factors that regulate PDK4 mRNA expression include plasma corticosterone, insulin and free fatty acids.
981	21162119	The model indicated that corticosterone had a moderate effect and PDK4 was more sensitive to free fatty acid than insulin fluxes, which was in good agreement with the literature data.
982	21321124	We sought to evaluate the metabolic and functional consequences of chronic suppression of GO in heart as modeled by transgenic mice with cardiac-specific overexpression of pyruvate dehydrogenase kinase 4 (myosin heavy chain (MHC)-PDK4 mice), an inhibitor of pyruvate dehydrogenase.
983	21321124	The expression of the known AMP-activated protein kinase target, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial function and biogenesis, was also activated in the MHC-PDK4 heart.
984	21904029	Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
985	21904029	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.
986	21904029	PDC activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms (PDK1-4), which phosphorylate and inactivate PDC.
987	21904029	ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, although both forms of PDK4 assume open conformations with a wider active-site cleft than that in the closed conformation of the previously reported ADP-bound PDK2 structure.
988	21904029	Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
989	21904029	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.
990	21904029	PDC activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms (PDK1-4), which phosphorylate and inactivate PDC.
991	21904029	ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, although both forms of PDK4 assume open conformations with a wider active-site cleft than that in the closed conformation of the previously reported ADP-bound PDK2 structure.
992	22019269	Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome.
993	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
994	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
995	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
996	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
997	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
998	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
999	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1000	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1001	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1002	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1003	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1004	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1005	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1006	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1007	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1008	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1009	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1010	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1011	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1012	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1013	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1014	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1015	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1016	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1017	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1018	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1019	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1020	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1021	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1022	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1023	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1024	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1025	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1026	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1027	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1028	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1029	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1030	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1031	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1032	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1033	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1034	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1035	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
1036	22698918	Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin.
1037	22698918	The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice.
1038	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
1039	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
1040	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
1041	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
1042	23066095	The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance.
1043	23066095	Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids.
1044	23066095	As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis.
1045	23066095	The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance.
1046	23066095	Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids.
1047	23066095	As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis.
1048	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
1049	23130316	The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes.
1050	23130316	Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear.
1051	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
1052	23130316	Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified.
1053	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
1054	23130316	In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
1055	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
1056	23130316	The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes.
1057	23130316	Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear.
1058	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
1059	23130316	Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified.
1060	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
1061	23130316	In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
1062	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
1063	23130316	The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes.
1064	23130316	Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear.
1065	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
1066	23130316	Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified.
1067	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
1068	23130316	In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
1069	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
1070	23130316	The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes.
1071	23130316	Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear.
1072	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
1073	23130316	Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified.
1074	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
1075	23130316	In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
1076	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
1077	23130316	The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes.
1078	23130316	Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear.
1079	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
1080	23130316	Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified.
1081	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
1082	23130316	In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
1083	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1084	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1085	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1086	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1087	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1088	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1089	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1090	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1091	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1092	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1093	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1094	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1095	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1096	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1097	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1098	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1099	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1100	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1101	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1102	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1103	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1104	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1105	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1106	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1107	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1108	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1109	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1110	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1111	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1112	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1113	23650578	Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
1114	23650578	Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression.
1115	23650578	Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel.
1116	23650578	This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation.
1117	23650578	In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation.
1118	23650578	Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a "thrifty" phenotype, favouring the development of obesity.
1119	23797112	Leelamine may be applicable to treat diabetes and is known to inhibit pyruvate dehydrogenase kinase 4.
1120	23842279	In the presence of PPARβ/δ, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1α leading to a 47% decrease in the activity of the pyruvate dehydrogenase complex in HepG2 cells.
1121	23842279	Vpr induced a 1.3-fold increase in mRNA expression of both carnitine palmitoyltransferase I (CPT1) and acetyl-coenzyme A acyltransferase 2 (ACAA2) and doubled the activity of β-hydroxylacyl coenzyme A dehydrogenase (HADH).
1122	23842279	The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and β-oxidation were reversed by specific PPARβ/δ antagonists.
1123	23940800	Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
1124	23940800	Pyruvate dehydrogenase kinases (PDK1-4) play a critical role in the inhibition of the mitochondrial pyruvate dehydrogenase complex especially when blood glucose levels are low and pyruvate can be conserved for gluconeogenesis.
1125	23940800	To address this question, we crossed Pdk2 or Pdk4 null mice with a diabetic model that is deficient in hepatic insulin receptor substrates 1 and 2 (Irs1/2).
1126	23940800	Metabolic analyses reveal that deletion of the Pdk4 gene had better improvement in hyperglycemia and glucose tolerance than knockout of the Pdk2 gene whereas the Pdk2 gene deletion showed better insulin tolerance as compared to the Pdk4 gene inactivation on the Irs1/2 knockout genetic background.
1127	23940800	To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs.
1128	23940800	The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.
1129	23940800	Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
1130	23940800	Pyruvate dehydrogenase kinases (PDK1-4) play a critical role in the inhibition of the mitochondrial pyruvate dehydrogenase complex especially when blood glucose levels are low and pyruvate can be conserved for gluconeogenesis.
1131	23940800	To address this question, we crossed Pdk2 or Pdk4 null mice with a diabetic model that is deficient in hepatic insulin receptor substrates 1 and 2 (Irs1/2).
1132	23940800	Metabolic analyses reveal that deletion of the Pdk4 gene had better improvement in hyperglycemia and glucose tolerance than knockout of the Pdk2 gene whereas the Pdk2 gene deletion showed better insulin tolerance as compared to the Pdk4 gene inactivation on the Irs1/2 knockout genetic background.
1133	23940800	To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs.
1134	23940800	The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.
1135	23940800	Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
1136	23940800	Pyruvate dehydrogenase kinases (PDK1-4) play a critical role in the inhibition of the mitochondrial pyruvate dehydrogenase complex especially when blood glucose levels are low and pyruvate can be conserved for gluconeogenesis.
1137	23940800	To address this question, we crossed Pdk2 or Pdk4 null mice with a diabetic model that is deficient in hepatic insulin receptor substrates 1 and 2 (Irs1/2).
1138	23940800	Metabolic analyses reveal that deletion of the Pdk4 gene had better improvement in hyperglycemia and glucose tolerance than knockout of the Pdk2 gene whereas the Pdk2 gene deletion showed better insulin tolerance as compared to the Pdk4 gene inactivation on the Irs1/2 knockout genetic background.
1139	23940800	To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs.
1140	23940800	The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.
1141	23940800	Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
1142	23940800	Pyruvate dehydrogenase kinases (PDK1-4) play a critical role in the inhibition of the mitochondrial pyruvate dehydrogenase complex especially when blood glucose levels are low and pyruvate can be conserved for gluconeogenesis.
1143	23940800	To address this question, we crossed Pdk2 or Pdk4 null mice with a diabetic model that is deficient in hepatic insulin receptor substrates 1 and 2 (Irs1/2).
1144	23940800	Metabolic analyses reveal that deletion of the Pdk4 gene had better improvement in hyperglycemia and glucose tolerance than knockout of the Pdk2 gene whereas the Pdk2 gene deletion showed better insulin tolerance as compared to the Pdk4 gene inactivation on the Irs1/2 knockout genetic background.
1145	23940800	To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs.
1146	23940800	The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.