scholarly journals Hepatic glycogen synthesis on carbohydrate re-feeding after starvation. A regulatory role for pyruvate dehydrogenase in liver and extrahepatic tissues

1986 ◽  
Vol 235 (2) ◽  
pp. 441-445 ◽  
Author(s):  
M J Holness ◽  
T J French ◽  
M C Sugden
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Synthesis ◽  
Regulatory Role ◽  
Hepatic Glycogen ◽  
Glucose Administration ◽  
Hepatic Glucose ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Dehydrogenase Complex

Glucose administration to 48 h-starved rats increased hepatic glucose, lactate, pyruvate and glycogen concentrations and re-activated PDH (pyruvate dehydrogenase complex) in kidney, but not in heart or liver. Dichloroacetate together with glucose re-activated PDH in all three tissues, decreased hepatic lactate and pyruvate concentrations and impaired glycogen resynthesis. Thus on re-feeding, delayed PDH re-activation is important for provision of precursors for hepatic glyconeogenesis.

scholarly journals Hepatic carbon flux after re-feeding. Hyperthyroidism blocks glycogen synthesis and the suppression of glucose output observed in response to carbohydrate re-feeding

1987 ◽  
Vol 247 (3) ◽  
pp. 627-634 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Intragastric Administration ◽  
Indirect Pathway ◽  
Glucose Flux ◽  
Glucose Output ◽  
Dehydrogenase Complex

1. The work investigated hepatic glycogen synthesis and glucose output after the intragastric administration of glucose or glycerol or the provision of chow ad libitum to 48 h-starved euthyroid or hyperthyroid rats. 2. After glucose administration, glycogen synthesis via the indirect pathway [Newgard, Hirsch, Foster & McGarry (1983) J. Biol. Chem. 258, 8046-8052] occurred concomitantly with reversal of glucose flux across the liver and re-activation of pyruvate kinase in the euthyroid controls. Glycogen synthesis was decreased and net glucose output continued in the hyperthyroid rats, but normal re-activation of pyruvate kinase was observed. 3. Use of 3-mercaptopicolinate indicated that the glucose released from liver of hyperthyroid rats was synthesized from substrates metabolized via the gluconeogenic pathway. 4. Hepatic glycogen synthesis was also impaired in hyperthyroid rats after administration of glycerol or chow. Measurement of portal-minus-hepatovenous concentration differences and arterial glucose concentrations after the administration of glycerol in combination with 3-mercaptopicolinate indicated that flux from triose phosphate to glucose 6-phosphate was not decreased. 5. Inhibited glycogen synthesis after chow re-feeding was associated with accelerated re-activation of hepatic pyruvate dehydrogenase complex in the hyperthyroid rats. 6. The results indicate three distinct and independent actions of hyperthyroidism after re-feeding: (i) it inhibits the reversal of glucose flux across the liver normally observed in response to carbohydrate; (ii) it affects glycogen deposition at a site distal to glucose 6-phosphate; (iii) it allows more rapid re-activation of liver pyruvate dehydrogenase complex in response to a mixed diet.

scholarly journals Hepatic carbon flux after re-feeding in the glycogen-storage-disease (gsd/gsd) rat

1987 ◽  
Vol 248 (3) ◽  
pp. 969-972 ◽  
Author(s):  
M J Holness ◽  
T N Palmer ◽  
E B Worrall ◽  
M C Sugden
Keyword(s):  
Glycogen Storage Disease ◽  
Pyruvate Dehydrogenase ◽  
Carbon Flux ◽  
Storage Disease ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Storage ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Dehydrogenase Complex

In this study we utilized the phosphorylase b kinase-deficient (gsd/gsd) rat as a model of hepatic substrate utilization where there is a constraint on glycogenesis imposed by the maintenance of high glycogen concentrations. Glucose re-feeding of 48 h-starved gsd/gsd rats led to suppression of hepatic glucose output. In contrast with the situation in normal rats, activation of the pyruvate dehydrogenase complex and lipogenesis was observed. It is suggested that impeding glycogenic flux may divert substrate into lipogenesis, possibly via activation of the pyruvate dehydrogenase complex.

scholarly journals Pyruvate dehydrogenase activities during the fed-to-starved transition and on re-feeding after acute or prolonged starvation

1989 ◽  
Vol 258 (2) ◽  
pp. 529-533 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Acute Phase ◽  
Pyruvate Dehydrogenase ◽  
Temporal Relationship ◽  
Pyruvate Dehydrogenase Complex ◽  
Hepatic Glycogen ◽  
Dietary Carbohydrate ◽  
Glycogen Depletion ◽  
Prolonged Starvation ◽  
Complex Activities ◽  
Dehydrogenase Complex

We investigated the temporal relationship between hepatic glycogen depletion and cardiac and hepatic PDH (pyruvate dehydrogenase complex) activities during the acute phase of starvation. There was a striking correlation between the decline in hepatic glycogen and PDH inactivation during the first 10 h of starvation. Re-feeding after 6 h starvation was associated with complete re-activation of PDH in liver and re-activation to approx. 75% of the fed value in heart, whereas in rats previously starved for 24-48 h re-activation was delayed in liver and diminished in heart. The results are discussed with reference to the fate of dietary carbohydrate after re-feeding.

scholarly journals Regulation of renal and hepatic pyruvate dehydrogenase complex on carbohydrate re-feeding after starvation. Possible mechanisms and a regulatory role for thyroid hormone

1987 ◽  
Vol 241 (2) ◽  
pp. 421-425 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Thyroid Hormone ◽  
Direct Effect ◽  
Pyruvate Dehydrogenase ◽  
Kinase Activity ◽  
Pyruvate Dehydrogenase Complex ◽  
Regulatory Role ◽  
Insulin Administration ◽  
Limited Effect ◽  
Blood Concentrations ◽  
Dehydrogenase Complex

The work investigated the mechanisms for modulation of renal and hepatic pyruvate dehydrogenase complex (PDH) activities after carbohydrate re-feeding of 48 h-starved rats, and identified a regulatory role for tri-iodothyronine. Glucose re-feeding decreased blood concentrations of lipid fuels in both euthyroid and hyperthyroid rats. This treatment was not associated with re-activation of hepatic PDH in either group of rats, or of renal PDH in hyperthyroid rats (where activity was already high), but it increased renal PDH in euthyroid rats. Dichloroacetate (DCA), an activator of PDH kinase, increased renal PDH activities in euthyroid rats, but not hyperthyroid rats, and effects of glucose re-feeding or hyperthyroidism were no longer apparent. These treatments therefore exert their effects on renal PDH through changes in PDH kinase. DCA re-activation of hepatic PDH was more marked in hyperthyroid than in euthyroid rats, suggesting that, under conditions of inhibited kinase activity, PDH phosphatase is more active in livers of hyperthyroid rats. The limited effect of DCA on hepatic PDH in euthyroid rats was potentiated by glucose re-feeding or insulin, but not by inhibition of lipolysis, demonstrating a direct effect of insulin to increase hepatic PDH phosphatase. Glucose re-feeding, inhibition of lipolysis or insulin administration did not increase hepatic PDH in DCA-treated hyperthyroid rats, indicating that effects of hyperthyroidism and of insulin on PDH phosphatase are not additive.

The Pyruvate Dehydrogenase Complex as a Target for Gene Therapy

2003 ◽  
Vol 3 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Peter Stacpoole ◽  
Renius Owen ◽  
Terence Flotte
Keyword(s):  
Gene Therapy ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Dehydrogenase Complex
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