Ignet

Gene Information

Gene symbol: PDHX

Gene name: pyruvate dehydrogenase complex, component X

HGNC ID: 21350

Synonyms: E3BP, proX, PDX1, OPDX, DLDBP

Related Genes

#	Gene Symbol	Number of hits
1	ACLY	1 hits
2	ACSS2	1 hits
3	BCKDHB	1 hits
4	COQ7	1 hits
5	CPT1A	1 hits
6	CPT2	1 hits
7	CRAT	1 hits
8	DLAT	1 hits
9	DLD	1 hits
10	FOXO1	1 hits
11	GIP	1 hits
12	GIPR	1 hits
13	INS	1 hits
14	NKX6-1	1 hits
15	NKX6-2	1 hits
16	PC	1 hits
17	PDC	1 hits
18	PDHB	1 hits
19	PDK1	1 hits
20	PDK2	1 hits
21	PDK3	1 hits
22	PDK4	1 hits
23	PDX1	1 hits
24	PPM2C	1 hits
25	SLC27A1	1 hits
26	SLC2A2	1 hits
27	SLC2A4	1 hits
28	SOD2	1 hits
29	TFAM	1 hits

Related Sentences

#	PMID	Sentence
1	212016	Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat.
2	212016	The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2.
3	212016	This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria.
4	212016	The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5.
5	212016	Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat.
6	212016	The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2.
7	212016	This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria.
8	212016	The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5.
9	212016	Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat.
10	212016	The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2.
11	212016	This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria.
12	212016	The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5.
13	231784	Regulation of pyruvate dehydrogenase by insulin action.
14	231784	In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase.
15	231784	The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P.
16	231784	Regulation of pyruvate dehydrogenase by insulin action.
17	231784	In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase.
18	231784	The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P.
19	373769	The pyruvate dehydrogenase complex is inhibited by products of its reactions; it is also regulated by a phosphorylation-dephosphorylation cycle catalysed by a kinase intrinsic to the complex and by a more loosely associated phosphatase.
20	373769	It is suggested that rates of oxidation of lipid fuels may be a major determinant of the activity of pyruvate dehydrogenase in tissues in relation to the actions of insulin and lipolytic hormones and the effects of diabetes and starvation.
21	631458	The effect of insulin on pyruvate dehydrogenase interconversion in heart muscle of alloxan-diabetic rats.
22	631458	Evidence is presented for regulation by insulin of pyruvate dehydrogenase (pdh) interconversion in rat heart muscle in vivo and in vitro.
23	631458	On perfusion of isolated hearts from diabetic rats in the presence of glucose the proportion of pyruvate dehydrogenase in the active form remained low but was fully restored upon addition of insulin (2mU/ml) to the medium.
24	631458	The correlation between the rate of pyruvate decarboxylation in the perfused heart and of pyruvate dehydrogenase activity, in vitro, suggests that in the diabetic heart the entry of pyruvate into the citric acid cycle is largely controlled by covalent modification of the pyruvate dehydrogenase complex rather than by feedback inhibition.
25	1269848	Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats.
26	1269848	Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats.
27	1269848	Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats.
28	1269848	Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats.
29	1592161	The insulin signal and its effects on the pyruvate dehydrogenase complex in circulating lymphocytes of obese children.
30	1592161	Studies have shown that in circulating lymphocytes pyruvate dehydrogenase (PDH) is responsive to insulin. 2.
31	2403034	Considerable sequence similarity is also apparent between the E1 alpha subunits of the human branched-chain alpha-ketoacid dehydrogenase complex and the pyruvate dehydrogenase complex.
32	2898264	The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered.
33	2898264	Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.
34	3715955	Dichloroacetate (DCA) is known to prevent the phosphorylation of the pyruvate dehydrogenase complex (PDHC) by blocking the action of PDH kinase.
35	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
36	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
37	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
38	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
39	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
40	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
41	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
42	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
43	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
44	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
45	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
46	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
47	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
48	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
49	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
50	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
51	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
52	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
53	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
54	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
55	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
56	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
57	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
58	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
59	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
60	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
61	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
62	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
63	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
64	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
65	3888756	Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
66	3888756	At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar.
67	3888756	The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05).
68	3888756	The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats.
69	3888756	Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01).
70	3888756	The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.
71	3902717	Effect of insulin on the pyruvate dehydrogenase complex in the rat brain.
72	3902717	PDHa and PDHt from alloxan rat brains are remarkably activated when assayed on samples obtained by combining and preincubating at 30 degrees C for 30 min a homogenate from fresh unfrozen brains of alloxan rats, with a similarly treated preparation from fresh unfrozen brains of normal or insulin rats.
73	3992045	Regulation of pyruvate dehydrogenase complex activity during myocardial ischemia.
74	4054446	Activity of the pyruvate dehydrogenase complex determines the rate of glucose oxidation in animals including man.
75	4054446	Activity is therefore dependent upon the activities of pyruvate dehydrogenase kinase and phosphatase.
76	4054446	The mechanism involves activation of pyruvate dehydrogenase kinase by short-term effects of products of fatty acid oxidation and by longer term effects involving specific protein synthesis; in hepatocytes the signals may include lipid fuels and glucagon.
77	6137008	The pyruvate dehydrogenase complex is almost totally inactivated (99%) by starvation or diabetes, the kinase reactions being accelerated by products of fatty acid oxidation and by a protein or protein-associated factor induced by starvation or diabetes.
78	6376223	Activation of pyruvate dehydrogenase complex by porcine and biosynthetic human insulin in cultured human fibroblasts.
79	6376223	We have investigated the properties of the pyruvate dehydrogenase multi-enzyme complex (PDC) and have studied the effects of various concentrations of porcine and biosynthetic human insulin (BHI) on the activity of the enzyme.
80	6481814	The effect of ischaemia on the activity of pyruvate dehydrogenase complex in rat heart.
81	6481814	The effect of ischaemia on the concentration of active pyruvate dehydrogenase complex has been investigated in glucose perfused hearts of normal rats fed a normal diet or a high fat diet or starved for 48 h; and in hearts from alloxan-diabetic rats.
82	6481814	Evidence is reviewed that the effects of low flow ischaemia, K+ arrest and anoxia may be mediated through activation of pyruvate dehydrogenase kinase by increased reduction of mitochondrial NAD+.
83	6481814	The effect of ischaemia on the activity of pyruvate dehydrogenase complex in rat heart.
84	6481814	The effect of ischaemia on the concentration of active pyruvate dehydrogenase complex has been investigated in glucose perfused hearts of normal rats fed a normal diet or a high fat diet or starved for 48 h; and in hearts from alloxan-diabetic rats.
85	6481814	Evidence is reviewed that the effects of low flow ischaemia, K+ arrest and anoxia may be mediated through activation of pyruvate dehydrogenase kinase by increased reduction of mitochondrial NAD+.
86	6618427	Change of skeletal muscles pyruvate dehydrogenase complex activities in congenital diabetic mice (KK mice) by aging or contraction.
87	6618427	The activity of pyruvate dehydrogenase complex was measured in skeletal muscle of congenital diabetic mice (KK mice) and control mice (ddN mice), each group in a starved or unstarved state, with or without muscular contraction.
88	6618427	The age related increment of the level of active form pyruvate dehydrogenase complex in KK mice was not found compared with that in ddN mice.
89	6618427	These results suggest that the activity of pyruvate dehydrogenase complex is intimately related to the onset of diabetes.
90	6618427	Change of skeletal muscles pyruvate dehydrogenase complex activities in congenital diabetic mice (KK mice) by aging or contraction.
91	6618427	The activity of pyruvate dehydrogenase complex was measured in skeletal muscle of congenital diabetic mice (KK mice) and control mice (ddN mice), each group in a starved or unstarved state, with or without muscular contraction.
92	6618427	The age related increment of the level of active form pyruvate dehydrogenase complex in KK mice was not found compared with that in ddN mice.
93	6618427	These results suggest that the activity of pyruvate dehydrogenase complex is intimately related to the onset of diabetes.
94	6618427	Change of skeletal muscles pyruvate dehydrogenase complex activities in congenital diabetic mice (KK mice) by aging or contraction.
95	6618427	The activity of pyruvate dehydrogenase complex was measured in skeletal muscle of congenital diabetic mice (KK mice) and control mice (ddN mice), each group in a starved or unstarved state, with or without muscular contraction.
96	6618427	The age related increment of the level of active form pyruvate dehydrogenase complex in KK mice was not found compared with that in ddN mice.
97	6618427	These results suggest that the activity of pyruvate dehydrogenase complex is intimately related to the onset of diabetes.
98	6618427	Change of skeletal muscles pyruvate dehydrogenase complex activities in congenital diabetic mice (KK mice) by aging or contraction.
99	6618427	The activity of pyruvate dehydrogenase complex was measured in skeletal muscle of congenital diabetic mice (KK mice) and control mice (ddN mice), each group in a starved or unstarved state, with or without muscular contraction.
100	6618427	The age related increment of the level of active form pyruvate dehydrogenase complex in KK mice was not found compared with that in ddN mice.
101	6618427	These results suggest that the activity of pyruvate dehydrogenase complex is intimately related to the onset of diabetes.
102	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
103	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
104	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
105	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
106	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
107	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
108	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
109	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
110	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
111	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
112	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
113	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
114	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
115	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
116	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
117	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
118	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
119	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
120	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
121	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
122	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
123	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
124	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
125	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
126	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
127	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
128	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
129	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
130	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
131	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
132	7021386	Short term regulation of mouse pyruvate dehydrogenase complex by insulin.
133	7021386	Pyruvate dehydrogenase complex activity and its regulating factors were measured in diabetic mice in a starved or unstarved state.
134	7021386	Both in starved and unstarved groups of normal mice, pyruvate dehydrogenase complex activity increased equally by insulin administration.
135	7021386	On the other hand, in an unstarved group of diabetic mice, no change in pyruvate dehydrogenase complex activity was observed with the same treatment.
136	7021386	As a result of studies on active form of pyruvate dehydrogenase complex in the liver and its regulating factors, it was found that no corresponding relation existed between the enzyme complex activity and its regulating factors.
137	7021386	We found that unlike the normal mice, not only the previously known regulating mechanism but also other factors affected the pyruvate dehydrogenase complex activity in the diabetic mice.
138	7159398	Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats.
139	7159398	Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats.
140	7159398	In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
141	7159398	Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats.
142	7159398	Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats.
143	7159398	In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
144	7396870	Incorporation of [32P]phosphate into the pyruvate dehydrogenase complex in rat heart mitochondria.
145	7396870	Evidence is given for three sites of phosphorylation in the alpha-chains of the decarboxylase component of purified rat heart pyruvate dehydrogenase complex, analogous to those established for procine and bovine complexes.
146	7396870	Incorporation of [32P]phosphate into the pyruvate dehydrogenase complex in rat heart mitochondria.
147	7396870	Evidence is given for three sites of phosphorylation in the alpha-chains of the decarboxylase component of purified rat heart pyruvate dehydrogenase complex, analogous to those established for procine and bovine complexes.
148	7470023	Effect of streptozotocin-induced diabetes mellitus on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase.
149	7470023	Immunochemical techniques were used to study the effect of streptozotocin-induced diabetes on the amounts of pyruvate carboxylase and pyruvate dehydrogenase and on their rates of synthesis and degradation.
150	7470023	Similar experiments with pyruvate dehydrogenase, the first component of the pyruvate dehydrogenase complex, showed that livers from diabetic rats had approximately the same amount of immunoprecipitable enzyme protein as the control animals, but a larger proportion of the enzyme was in its inactive state.
151	7572341	Two isoforms of pyruvate dehydrogenase kinase have been identified and cloned.
152	7572341	Pyruvate dehydrogenase kinase 1, the first isoform cloned, corresponds to the 48 kDa subunit of the pyruvate dehydrogenase kinase isolated from rat heart tissue.
153	7572341	Pyruvate dehydrogenase kinase 2, the second isoform cloned, corresponds to the 45 kDa subunit of this enzyme.
154	7572341	In addition, it also appears to correspond to a possibly free or soluble form of pyruvate dehydrogenase kinase that was originally named kinase activator protein.
155	7572341	Assuming that differences in kinetic and/or regulatory properties of these isoforms exist, tissue specific expression of these enzymes and/or control of their association with the complex will probably prove to be important for the long term regulation of the activity of the pyruvate dehydrogenase complex.
156	7572341	Starvation and the diabetic state are known to greatly increase activity of the pyruvate dehydrogenase kinase in the liver, heart and muscle of the rat.
157	7572341	This contributes in these states to the phosphorylation and inactivation of the pyruvate dehydrogenase complex and conservation of pyruvate and lactate for gluconeogenesis.
158	7572341	Two isoforms of pyruvate dehydrogenase kinase have been identified and cloned.
159	7572341	Pyruvate dehydrogenase kinase 1, the first isoform cloned, corresponds to the 48 kDa subunit of the pyruvate dehydrogenase kinase isolated from rat heart tissue.
160	7572341	Pyruvate dehydrogenase kinase 2, the second isoform cloned, corresponds to the 45 kDa subunit of this enzyme.
161	7572341	In addition, it also appears to correspond to a possibly free or soluble form of pyruvate dehydrogenase kinase that was originally named kinase activator protein.
162	7572341	Assuming that differences in kinetic and/or regulatory properties of these isoforms exist, tissue specific expression of these enzymes and/or control of their association with the complex will probably prove to be important for the long term regulation of the activity of the pyruvate dehydrogenase complex.
163	7572341	Starvation and the diabetic state are known to greatly increase activity of the pyruvate dehydrogenase kinase in the liver, heart and muscle of the rat.
164	7572341	This contributes in these states to the phosphorylation and inactivation of the pyruvate dehydrogenase complex and conservation of pyruvate and lactate for gluconeogenesis.
165	7669066	Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex.
166	7669066	The stereoselectivity and specificity of lipoic acid for the pyruvate dehydrogenase complex and its component enzymes from different sources has been studied.
167	7669066	Dihydrolipoamide dehydrogenase from human renal carcinoma has a higher Michaelis constant for R-lipoic acid (Km = 18 mM) and does not accept the S-enantiomer as a substrate.
168	7669066	Both enantiomers of lipoic acid are inhibitors of the overall reaction of the bovine pyruvate dehydrogenase complex, but stimulate the respective enzyme complexes from rat as well as from Escherichia coli.
169	7669066	Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex.
170	7669066	The stereoselectivity and specificity of lipoic acid for the pyruvate dehydrogenase complex and its component enzymes from different sources has been studied.
171	7669066	Dihydrolipoamide dehydrogenase from human renal carcinoma has a higher Michaelis constant for R-lipoic acid (Km = 18 mM) and does not accept the S-enantiomer as a substrate.
172	7669066	Both enantiomers of lipoic acid are inhibitors of the overall reaction of the bovine pyruvate dehydrogenase complex, but stimulate the respective enzyme complexes from rat as well as from Escherichia coli.
173	7669066	Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex.
174	7669066	The stereoselectivity and specificity of lipoic acid for the pyruvate dehydrogenase complex and its component enzymes from different sources has been studied.
175	7669066	Dihydrolipoamide dehydrogenase from human renal carcinoma has a higher Michaelis constant for R-lipoic acid (Km = 18 mM) and does not accept the S-enantiomer as a substrate.
176	7669066	Both enantiomers of lipoic acid are inhibitors of the overall reaction of the bovine pyruvate dehydrogenase complex, but stimulate the respective enzyme complexes from rat as well as from Escherichia coli.
177	7722501	The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased.
178	7722501	The specific activities of two other mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic enzyme--lactate dehydrogenase--are unaltered.
179	7821731	This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex.
180	7821731	Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate.
181	7821731	This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex.
182	7821731	Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate.
183	7882173	It is clear that an increase in intramitochondrial acetyl-CoA derived from carbohydrate oxidation (via the pyruvate dehydrogenase complex) can downregulate beta-oxidation of fatty acids, but it is not clear how fatty acid acyl group entry into the mitochondria is downregulated when carbohydrate oxidation increases.
184	7882173	While it has been known for some time that malonyl-CoA does exist in heart tissue, and that it is a potent inhibitor of carnitine palmitoyltransferase 1 (CPT 1), it has only recently been demonstrated that an isoenzyme of ACC exists in the heart that is a potential source of malonyl-CoA.
185	7952850	Among hereditary defects of nuclear-encoded mitochondrial enzymes, carnitine palmitoyltransferase II (CPT-II) deficiency and pyruvate dehydrogenase complex (PDHC) deficiency are of major interest to the neurologist.
186	7952850	MELAS, MERRF, NARP, MIMyCa, etc.), 'pure' encephalopathies (e.g.
187	8240285	Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice.
188	8240285	The diurnal pattern of the activity of the pyruvate dehydrogenase complex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG)-obese mice and age-matched controls.
189	8240285	Diurnal patterns of cardiac and hepatic pyruvate dehydrogenase complex activity in gold-thioglucose-obese mice.
190	8240285	The diurnal pattern of the activity of the pyruvate dehydrogenase complex (PDHC) was studied in the heart and liver of gold-thioglucose (GTG)-obese mice and age-matched controls.
191	8492717	Insulin-induced activation of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats.
192	8492717	The pyruvate dehydrogenase (PDH) complex undergoes reversible phosphorylation catalyzed by a PDH kinase (inactivating) and a PDH phosphatase (activating).
193	8492717	In skeletal muscle, a decreased proportion of active PDH (PDHa) complex limits glucose oxidation in insulin-deficient states.
194	8492717	The time-course for reactivation of the PDH complex by insulin in skeletal muscle of diabetic rats is important to understanding the potential mode of the action of insulin in regulating glucose metabolism.
195	8492717	A single injection of insulin (1 U/kg) completely reversed the effects of alloxan-diabetes on PDHa activity within 1 hour.
196	8492717	The normalization of the effects of diabetes on PDHa activity by insulin was maintained for a minimum of 6 hours.
197	8492717	The increase in PDHa activity occurred before an insulin-induced decrease in plasma free fatty acids levels, demonstrating a dissociation between the antilipolytic effects of insulin and its ability to activate the PDH complex.
198	8492717	Therefore, acute (1 to 6 hours) insulin-mediated activation of the PDH complex does not result from a decrease in PDH kinase activity.
199	8492717	However, longer-term insulin therapy (1 U/kg body weight; twice daily) restored both PDHa and PDH kinase activities.
200	8492717	The results are consistent with the hypothesis that activation of the PDH complex immediately following insulin administration is not mediated by a decreased PDH kinase activity.
201	8492717	However, with daily insulin therapy in diabetes, activation of the PDH complex results from decreased PDH kinase activity.
202	8638694	Euglycemic and hyperglycemic clamp experiments were performed with somatostatin infusions so that insulin could be replaced to basal levels or to physiological hyperinsulinemia.
203	8638694	Percutaneous biopsies of the vastus lateralis muscle were taken to determine the pyruvate dehydrogenase complex or glycogen synthase activities.
204	8798399	Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
205	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.
206	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.
207	8805794	The conversion of pyruvate to acetyl CoA (aerobic metabolism) involves a series of chain reactions primarily catalyzed by pyruvate dehydrogenase complex which is situated at the cross roads between both aerobic and anaerobic glycolysis.
208	8995532	Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA dehydrogenase in sand rat (Psammomys obesus).
209	8995532	The total activity of liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats.
210	8995532	Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver pyruvate dehydrogenase complex and in increasing the activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.
211	8995532	Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA dehydrogenase in sand rat (Psammomys obesus).
212	8995532	The total activity of liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats.
213	8995532	Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver pyruvate dehydrogenase complex and in increasing the activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.
214	8995532	Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA dehydrogenase in sand rat (Psammomys obesus).
215	8995532	The total activity of liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats.
216	8995532	Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver pyruvate dehydrogenase complex and in increasing the activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.
217	9381974	Four members of this unique family of eukaryotic protein kinases correspond to pyruvate dehydrogenase kinase isozymes which regulate the activity of the pyruvate dehydrogenase complex, an important regulatory enzyme at the interface between glycolysis and the citric acid cycle.
218	9381974	The isoenzymes of pyruvate dehydrogenase kinase differ greatly in terms of their specific activities, kinetic parameters and regulatory properties.
219	9381974	Chemically-induced diabetes in the rat induces significant changes in the pyruvate dehydrogenase kinase isoenzyme 2 in liver.
220	9381974	Preliminary findings suggest hormonal control of the activity state of the pyruvate dehydrogenase complex may involves tissue specific induced changes in expression of the pyruvate dehydrogenase kinase isoenzymes.
221	9381974	Four members of this unique family of eukaryotic protein kinases correspond to pyruvate dehydrogenase kinase isozymes which regulate the activity of the pyruvate dehydrogenase complex, an important regulatory enzyme at the interface between glycolysis and the citric acid cycle.
222	9381974	The isoenzymes of pyruvate dehydrogenase kinase differ greatly in terms of their specific activities, kinetic parameters and regulatory properties.
223	9381974	Chemically-induced diabetes in the rat induces significant changes in the pyruvate dehydrogenase kinase isoenzyme 2 in liver.
224	9381974	Preliminary findings suggest hormonal control of the activity state of the pyruvate dehydrogenase complex may involves tissue specific induced changes in expression of the pyruvate dehydrogenase kinase isoenzymes.
225	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
226	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.
227	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.
228	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.
229	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.
230	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.
231	9405294	Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
232	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.
233	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.
234	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.
235	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.
236	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.
237	9688898	Furthermore, hearts from diabetic animals showed a marked dependence on fatty acids for substrate utilization compared with nondiabetic controls, consistent with inhibition of the pyruvate dehydrogenase complex in diabetic hearts.
238	9729480	Heterologously expressed inner lipoyl domain of dihydrolipoyl acetyltransferase inhibits ATP-dependent inactivation of pyruvate dehydrogenase complex.
239	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
240	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
241	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.
242	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.
243	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.
244	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.
245	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.
246	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.
247	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.
248	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
249	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
250	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.
251	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.
252	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.
253	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.
254	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.
255	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.
256	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.
257	10426378	Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.
258	10426378	Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis.
259	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.
260	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.
261	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.
262	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.
263	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.
264	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.
265	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.
266	10509817	These alignments were validated by testing all of the 53 phagotopes derived using IgG from PBC sera for reactivity by capture ELISA with antibodies affinity purified on the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major autoantigen in PBC: only those phagotopes that aligned to PBC-associated clusters were reactive.
267	10607479	Measurements have been made, in adult male diabetic patients and control subjects, of the urinary content of inositol phosphoglycans (IPGs), the IPG A-type and IPG P-type forms, which, among other actions, regulate pathways of glucose utilization, lipogenesis, triglyceride formation, and pyruvate dehydrogenase (PDH) activity.
268	10607479	In vitro studies of the effects of alterations in the IPG P-type:IPG A-type ratio on the activation of the pyruvate dehydrogenase complex (PDH complex) at the PDH phosphatase reaction demonstrated that IPG A-type forms antagonized the stimulation of the PDH phosphatase by IPG P-type forms, thus having a negative effect on the conversion of PDH to the active, dephosphorylated, form.
269	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.
270	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.
271	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.
272	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.
273	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.
274	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.
275	11054649	Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.
276	11054649	The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC).
277	11356166	Because its activity can either determine or reflect fuel preference (carbohydrate versus fat), the pyruvate dehydrogenase complex (PDC) occupies a pivotal position in fuel cross-talk.
278	11456300	Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations.
279	11642366	Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms.
280	11642366	The mammalian pyruvate dehydrogenase complex (PDC) plays central and strategic roles in the control of the use of glucose-linked substrates as sources of oxidative energy or as precursors in the biosynthesis of fatty acids.
281	11642366	The activity of this mitochondrial complex is regulated by the continuous operation of competing pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) reactions.
282	11642366	The dihydrolipoyl acetyltransferase (E2) and the dihydrolipoyl dehydrogenase-binding protein (E3BP) are multidomain proteins that form the oligomeric core of the complex.
283	11642366	Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms.
284	11642366	The mammalian pyruvate dehydrogenase complex (PDC) plays central and strategic roles in the control of the use of glucose-linked substrates as sources of oxidative energy or as precursors in the biosynthesis of fatty acids.
285	11642366	The activity of this mitochondrial complex is regulated by the continuous operation of competing pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) reactions.
286	11642366	The dihydrolipoyl acetyltransferase (E2) and the dihydrolipoyl dehydrogenase-binding protein (E3BP) are multidomain proteins that form the oligomeric core of the complex.
287	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.
288	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.
289	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.
290	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.
291	11697863	In striking contrast, renal protein expression of PDK4 was only marginally induced by fasting in PPAR alpha null mice.
292	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.
293	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.
294	11723055	The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism.
295	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.
296	11723055	Rat islets were demonstrated to contain all three PDK isoforms, PDK1, PDK2, and PDK4.
297	11723055	Protein expression of PDK1 and PDK2 was suppressed in response to starvation (by 27% [P < 0.01] and 10% [NS], respectively).
298	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.
299	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.
300	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.
301	11723055	PPAR-alpha activation in vivo led to increased insulin secretion at low glucose concentrations.
302	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.
303	11812733	Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.
304	11812733	Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC).
305	11812733	Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes.
306	11812733	Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells.
307	11812733	The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels.
308	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.
309	11812733	Insulin also decreased the abundance of the PDK2 message.
310	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.
311	11812733	The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.
312	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.
313	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.
314	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.
315	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.
316	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.
317	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.
318	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).
319	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.
320	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.
321	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).
322	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.
323	12099888	Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression.
324	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.
325	12099888	Paradoxically, chronic activation of PPARalpha by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats.
326	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.
327	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.
328	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.
329	12149437	Analysis revealed a coordinated regulation at key steps in glucose and lipid metabolism, mitochondrial electron transport, transcriptional regulation, and protein trafficking. mRNAs for all of the enzymes of the fatty acid beta-oxidation pathway were increased, whereas those for GLUT4, hexokinase II, the E1 component of the pyruvate dehydrogenase complex, and subunits of all four complexes of the mitochondrial electron transport chain were all coordinately down-regulated.
330	12435272	Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.
331	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).
332	12435272	Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha).
333	12435272	Enhanced expression of PDK4, but not PDK2, occurs in part via a mechanism involving PPAR-alpha.
334	12435272	High-fat feeding increased hepatic PDK2, but not PDK4, protein expression whereas hyperthyroidism increased both hepatic PDK2 and PDK4 protein expression.
335	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.
336	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.
337	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.
338	12476789	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate, and links glycolysis to the tricarboxylic acid cycle and ATP production.
339	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.
340	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.
341	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.
342	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.
343	12476789	Factors that regulate PDK4 expression include FA oxidation and adequate insulin action.
344	12476789	PDK4 is also either a direct or indirect target of peroxisome proliferator-activated receptor (PPAR) alpha.
345	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.
346	12507273	Exercise training increases the activity of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats.
347	12633610	Immunocapture and microplate-based activity measurement of mammalian pyruvate dehydrogenase complex.
348	12633610	Altered pyruvate dehydrogenase (PDH) functioning occurs in primary PDH deficiencies and in diabetes, starvation, sepsis, and possibly Alzheimer's disease.
349	12676647	Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.
350	12676647	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid (FA) synthesis.
351	12676647	Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.
352	12676647	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid (FA) synthesis.
353	12765946	Starvation and diabetes reduce the amount of pyruvate dehydrogenase phosphatase in rat heart and kidney.
354	12765946	The pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes to conserve three-carbon compounds for gluconeogenesis.
355	12765946	This is achieved by an increase in the extent of PDC phosphorylation caused in part by increased pyruvate dehydrogenase kinase (PDK) activity due to increased PDK expression.
356	12765946	This study examined whether altered pyruvate dehydrogenase phosphatase (PDP) expression also contributes to changes in the phosphorylation state of PDC during starvation and diabetes.
357	14607783	Increased levels of manganese superoxide dismutase suggest that an antioxidant response has been mounted, and hydroxynonenal (HNE) modification of pyruvate dehydrogenase E2-(catalytic) and E3-binding protein subunits suggests that HNE-induced inactivation of this key enzyme may play a role in the mechanism of injury.
358	14641014	Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation.
359	14641014	PDC (pyruvate dehydrogenase complex) catalyses the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle.
360	14641014	Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation.
361	14641014	PDC (pyruvate dehydrogenase complex) catalyses the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle.
362	14644048	Characterization of the isozymes of pyruvate dehydrogenase phosphatase: implications for the regulation of pyruvate dehydrogenase activity.
363	14644048	The activity of mammalian pyruvate dehydrogenase complex (PDC) is regulated by a phosphorylation/dephosphorylation cycle.
364	14644048	Dephosphorylation accompanied by activation is carried out by two genetically different isozymes of pyruvate dehydrogenase phosphatase, PDP1c and PDP2c.
365	15047604	Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.
366	15047604	Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex.
367	15047604	Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied.
368	15047604	Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect.
369	15047604	Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect.
370	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.
371	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.
372	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.
373	15047604	Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors.
374	15075342	Coenzyme Q(0) (Q(0)), a strong electrophile, is toxic to insulin-producing cells.
375	15075342	Western analysis also showed that Q bonds to the E2 components of the purified KDC and (0)the pyruvate dehydrogenase complex (PDC).
376	15151993	Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets.
377	15151993	Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes.
378	15151993	To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1.
379	15151993	To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets.
380	15151993	In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
381	15151993	Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets.
382	15151993	Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes.
383	15151993	To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1.
384	15151993	To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets.
385	15151993	In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
386	15151993	Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets.
387	15151993	Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes.
388	15151993	To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1.
389	15151993	To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets.
390	15151993	In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
391	15151993	Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets.
392	15151993	Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes.
393	15151993	To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1.
394	15151993	To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets.
395	15151993	In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
396	15151993	Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets.
397	15151993	Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes.
398	15151993	To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1.
399	15151993	To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets.
400	15151993	In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion.
401	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.
402	15312755	The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible oxidative decarboxylation of pyruvate in mitochondria.
403	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.
404	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.
405	15312755	The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible oxidative decarboxylation of pyruvate in mitochondria.
406	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.
407	15703165	At that time, a marked increase of triglyceride content in gastronemius muscle was accompanied by a diminished activity of pyruvate dehydrogenase complex, suggesting an impaired glucose oxidation.
408	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.
409	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.
410	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
411	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.
412	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
413	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.
414	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
415	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.
416	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
417	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.
418	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.
419	15967803	Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
420	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.
421	15967803	The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation.
422	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.
423	15967803	Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression.
424	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.
425	15967803	Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo.
426	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.
427	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.
428	16483874	Pyruvate dehydrogenase kinase activity and abundance of PDK2 and PDK4 proteins, as well as mRNAs, were greater in OLETF rats at both ages.
429	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.
430	17079227	Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.
431	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.
432	17079227	Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity.
433	17079227	In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma).
434	17079227	Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4.
435	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.
436	17079227	In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter.
437	17079227	Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma.
438	17079227	The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha.
439	17079227	Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter.
440	17127716	Lipoic acid (LA) is a sulfated antioxidant produced physiologically as a coenzyme of the pyruvate dehydrogenase complex; it is currently used for treatment of non-insulin-dependent diabetes to favor the cellular uptake of glucose.
441	17127716	LA induced the production of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) in KS-Imm and activin-A in KS-Imm and endothelial cells; these factors show anti-angiogenic activity in vivo contributing to explain the inhibitory effect of LA on neovascularization.
442	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).
443	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.
444	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.
445	17158802	Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
446	17158802	Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin.
447	17158802	Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways.
448	17158802	Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses.
449	17158802	Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1.
450	17158802	Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
451	17158802	Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin.
452	17158802	Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways.
453	17158802	Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses.
454	17158802	Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1.
455	17158802	Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
456	17158802	Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin.
457	17158802	Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways.
458	17158802	Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses.
459	17158802	Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1.
460	17310282	Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.
461	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).
462	18658136	Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
463	18658136	Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4.
464	18805359	In the majority of cases, dysfunction of the respiratory chain (particularly complexes I, II, IV, or V), of coenzyme Q, or of the pyruvate dehydrogenase complex are responsible for the disease.
465	19361580	FATP1 localizes to mitochondria and enhances pyruvate dehydrogenase activity in skeletal myotubes.
466	19361580	FATP1 raises the activity and activates the pyruvate dehydrogenase (PDH) complex and the pyruvate decarboxylase PDH-E1 catalytic subunit, without changing E2, E3BP or E1alpha and increasing E1beta protein content.
467	21076574	Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels.
468	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.
469	21904029	Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
470	21904029	The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.
471	21904029	PDC activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms (PDK1-4), which phosphorylate and inactivate PDC.
472	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.
473	21934355	The pyruvate carboxylase-pyruvate dehydrogenase axis in islet pyruvate metabolism: Going round in circles?
474	21934355	The alternative fate of pyruvate is its oxidative decarboxylation to form acetyl-CoA via the pyruvate dehydrogenase complex (PDC).
475	22393382	Interestingly, they maintained expression of β-cell specific markers, such as PDX1, NKX6.1, GLUT2 and insulin.
476	22393382	Gene expression analysis showed that β-TC3R cells were characterized by downregulation of IL-1β and IFN-γ receptors and upregulation of SOCS3, the classical negative regulator of cytokines signaling.
477	22393382	Among them, SUMO4, a negative feedback regulator in NF-kB and JAK/STAT signaling pathways, resulted hyper-expressed.
478	22393382	Silencing of SUMO4 was able to restore sensitivity to cytokine-induced cell death in β-TC3R cells, suggesting it may play a key role in acquired cytokine resistance by blocking JAK/STAT and NF-kB lethal signaling.In conclusion, our study represents the first extensive proteomic characterization of a murine cytokine-resistant β-cell line, which might represent a useful tool for studying the mechanisms involved in resistance to cytokine-mediated β-cell death.
479	22698918	Metformin inhibits growth hormone-mediated hepatic PDK4 gene expression through induction of orphan nuclear receptor small heterodimer partner.
480	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.
481	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.
482	22698918	Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation.
483	22698918	Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction.
484	22698918	In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression.
485	22698918	SHP directly inhibited STAT5 association on the PDK4 gene promoter.
486	22896851	The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.
487	23130316	Transcriptional regulation of pyruvate dehydrogenase kinase.
488	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.
489	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.
490	23130316	Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway.
491	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.
492	23130316	It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners.
493	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.
494	23788637	We have used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPARγ expression in β-cells, thus transcription of its target genes (Pdx1, glucose-dependent insulinotropic polypeptide (GIP) receptor, and pyruvate carboxylase) that are important regulators of β-cell function, survival, and compensation.
495	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.
496	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).
497	23842279	The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and β-oxidation were reversed by specific PPARβ/δ antagonists.
498	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.
499	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).
500	23842279	The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and β-oxidation were reversed by specific PPARβ/δ antagonists.
501	23940800	Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
502	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.
503	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).
504	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.
505	23940800	To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs.
506	23940800	The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown.