Time-Course of Changes in Blood Glucose and Ketone Bodies, Plasma Lipids and Liver Fatty Acid Composition in Streptozotocin-Diabetic Male Rats

Topping, David L.; Targ, Michael E.

doi:10.1159/000178670

Cited by 15 publications

(9 citation statements)

References 13 publications

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“…In 6-weekold streptozotocin-diabetic rats, many of the hepatic enzymes involved in the regulation of lipid metabolism are suppressed [17,[26][27][28]. In these insulin-deficient animals, blood glucose levels and fatty acid levels rise [21], which was confirmed by our results ( Table 2). Although clearly diabetic (i.e.…”

Section: Discussionsupporting

confidence: 83%

“…In contrast with this, the levels of glucose in the serum were unaltered in the Cp\Cp rats as compared with the lean controls. These changes in glucose and fatty acid levels in the serum are consistent with the pathophysiology of these animals [14,21,22].…”

Section: Role Of MCD In Controlling Fatty Acid Metabolismsupporting

confidence: 65%

“…One explanation for this may be the dependence of plasma glucose levels on the feeding state of the animal and time of day when the animal was killed. Nevertheless, in livers where glucose uptake is not dependent on insulin, the tissue is exposed to abnormally high levels of glucose [21]. The liver responds to this increase in glucose by inactivating ACC [5], resulting in a decrease in the production of malonyl-CoA.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism

et al. 2000

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In the liver, malonyl-CoA is central to many cellular processes, including both fatty acid biosynthesis and oxidation. Malonyl-CoA decarboxylase (MCD) is involved in the control of cellular malonyl-CoA levels, and functions to decarboxylate malonyl-CoA to acetyl-CoA. MCD may play an essential role in regulating energy utilization in the liver by regulating malonyl-CoA levels in response to various nutritional or pathological states. The purpose of the present study was to investigate the role of liver MCD in the regulation of fatty acid oxidation in situations where lipid metabolism is altered. A single MCD enzyme of molecular mass 50.7 kDa was purified from rat liver using a sequential column chromatography procedure and the cDNA was subsequently cloned and sequenced. The liver MCD cDNA was identical to rat pancreatic beta-cell MCD cDNA, and contained two potential translational start sites, producing proteins of 50.7 kDa and 54.7 kDa. Western blot analysis using polyclonal antibodies generated against rat liver MCD showed that the 50.7 kDa isoform of MCD is most abundant in heart and liver, and of relatively low abundance in skeletal muscle (despite elevated MCD transcript levels in skeletal muscle). Tissue distribution experiments demonstrated that the pancreas is the only rat tissue so far identified that contains both the 50.7 kDa and 54. 7 kDa isoforms of MCD. In addition, transfection of the full-length rat liver MCD cDNA into COS cells produced two isoforms of MCD. This indicated either that both initiating methionines are functionally active, generating two proteins, or that the 54.7 kDa isoform is the only MCD protein translated and removal of the putative mitochondrial targeting pre-sequence generates a protein of approx. 50.7 kDa in size. To address this, we transiently transfected a mutated MCD expression plasmid (second ATG to GCG) into COS-7 cells and performed Western blot analysis using our anti-MCD antibody. Western blot analysis revealed that two isoforms of MCD were still present, demonstrating that the second ATG may not be responsible for translation of the 50.7 kDa isoform of MCD. These data also suggest that the smaller isoform of MCD may originate from intracellular processing. To ascertain the functional role of the 50. 7 kDa isoform of rat liver MCD, we measured liver MCD activity and expression in rats subjected to conditions which are known to alter fatty acid metabolism. The activity of MCD was significantly elevated under conditions in which hepatic fatty acid oxidation is known to increase, such as streptozotocin-induced diabetes or following a 48 h fast. A 2-fold increase in expression was observed in the streptozotocin-diabetic rats compared with control rats. In addition, MCD activity was shown to be enhanced by alkaline phosphatase treatment, suggesting phosphorylation-related control of the enzyme. Taken together, our data demonstrate that rat liver expresses a 50.7 kDa form of MCD which does not originate from the second methionine of the cDNA sequence. This MCD is regulated ...

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Section: Discussionsupporting

confidence: 83%

Section: Role Of MCD In Controlling Fatty Acid Metabolismsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism

et al. 2000

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“…In contrast to the difficulties encountered in trying to induce alloxan-diabetes in neonatal rats (15), streptozotocin produces a rapid and reproduc ible diabetic state in both weanling animals (this study) and animals of other ages (9,11,13) . The concentration of streptozotocin needed to produce diabetes in the weanling rat (225 mg/kg) was much higher than that general ly used for adult rats (50-100 mg/kg) (4,11,14) . The difference may reflect a greater resis tance of the young pancreas to streptozotocin or may indicate, as found for the fetus and neonate (9), that the young rat has an impres sive ability for regeneration of pancreatic tissue.…”

Section: Resultsmentioning

confidence: 84%

Effect of Streptozotocin Diabetes and Insulin Administration on Some Liver Enzyme Activities in the Post-Weaning Rat

Storey¹,

Bailey²

1978

Enzyme

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Streptozotocin-induced diabetes suppressed the normal development of the nine glycolytic and lipogenic enzyme activities measured. With the exception of NADP-isocitrate dehydrogenase, insulin replacement therapy induced increased activities of the enzymes in streptozotocin-treated rats. Insulin appeared to have a specific effect on the activities of glucokinase, ATP-citrate lyase, malic enzyme, and glucose-6-P-dehydrogenase.

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“…P-hydroxybutyrate gave about the 5ame ATPconcentration in diabetic aorta as the substrate mixture while a reduced ATP-concentration was found with the other substrates. The oxidation of P-hydroxybutyrate in rat aorta is concentration dependent (Dahlkvist & Arnqvist, unpublished results) and in diabetic, rats the plasma concentration of ketone bodies is increased about 10-fold (Topping & Targ 1975). Since P-hydroxybutyrate produced the highest ATP-concentration in diabetic aorta it seems probable that ketone bodies are the most important fuel for energy production in diabetic vascular tissue.…”

Section: Meankse (N=10)mentioning

confidence: 96%

Influence of exogenous substrates on adenosinetriphosphate (ATP) concentration in normal and diabetic rat aorta in vitro

Carlsson

Arnqvist

1981

Acta Physiologica Scandinavica

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In diabetic rat aorta glucose metabolism is impaired and changes in the activities of several enzymes are found. The aim of this study was to investigate whether the metabolic alterations in diabetic vascular tissue influence energy production. Aortas of normal and diabetic male Sprague-Dawley rats were incubated in vitro for up to 120 min with various substrates added to the incubation medium. Diabetes was induced by streptozotocin and the rats were used after a diabetes duration of two weeks. When normal and diabetic aorta were incubated in the presence of 5.6 mmol/l glucose no significant difference in ATP-concentration was found after 60 min while after 120 min the ATP-concentration was lowered in diabetic aorta. Addition to the incubation medium of a substrate mixture containing amino acids in the same concentrations as in rat plasma, 3 mmol/l DL-beta-hydroxybutyrate and 1.5 mmol/l palmitate increased the ATP-concentration, measured after 120 min, in diabetic aorta but not in normal aorta. No significant difference in ATP-concentration was found between normal and diabetic aorta incubated in a medium containing all substrates. When diabetic aorta was incubated with each substrate separately beta-hydroxybutyrate but not glucose, palmitate or amino acids, increased the ATP-concentration to about the same level as the complete substrate mixture. The results suggest that the ability to utilize glucose for ATP production is impaired in diabetic vascular tissue and that other substrates such as ketone bodies are of importance for energy production in diabetic vessels.

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Time-Course of Changes in Blood Glucose and Ketone Bodies, Plasma Lipids and Liver Fatty Acid Composition in Streptozotocin-Diabetic Male Rats

Cited by 15 publications

References 13 publications

Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism

Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism

Effect of Streptozotocin Diabetes and Insulin Administration on Some Liver Enzyme Activities in the Post-Weaning Rat

Influence of exogenous substrates on adenosinetriphosphate (ATP) concentration in normal and diabetic rat aorta in vitro

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