Physical training reverses defect in 3-ketoacid CoA-transferase activity in skeletal muscle of diabetic rats

2005 ◽  
Vol 288 (4) ◽  
pp. E748-E752 ◽  
Author(s):  
Adil El Midaoui ◽  
Jean Louis Chiasson ◽  
Gilles Tancrède ◽  
André Nadeau
Keyword(s):  
Skeletal Muscle ◽  
Plasma Concentration ◽  
Physical Training ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Transferase Activity ◽  
Hydroxybutyric Acid ◽  
Beneficial Effects ◽  
Coa Transferase ◽  
Key Enzyme

To investigate one potential mechanism whereby physical training improves the plasma concentration of ketone bodies in experimental diabetes mellitus, we measured the activity of 3-ketoacid CoA-transferase, the key enzyme in the peripheral utilization of ketone bodies. Diabetes was induced with streptozotocin (50 mg/kg) and training carried out on a treadmill with a progressive 10-wk program. Diabetes resulted in an increase ( P < 0.001) in plasma concentration of β-hydroxybutyric acid in sedentary rats, which was partly reversed by training ( P < 0.001). Diabetes was also associated with a decreased activity of 3-ketoacid CoA-transferase in gastrocnemius muscle. When expressed per total gastrocnemius, training increased the activity of 3-ketoacid CoA-transferase by 66% in nondiabetic rats ( P < 0.001) and by 150% in diabetic rats ( P < 0.001), the decrease present in diabetic rats being fully reversed by training. Simple linear regression between the log of 3-ketoacid CoA-transferase activity and the log of plasma β-hydroxybutyric acid levels showed a statistically significant ( r = 0.563, P < 0.001) negative correlation. The beneficial effects of training on plasma ketone bodies in diabetic rats are probably explained, at least in part, by an increase in ketone body utilization, mediated by an increase in skeletal muscle 3-ketoacid CoA-transferase activity.

Physical training reverses the increased activity of the hepatic ketone body synthesis pathway in chronically diabetic rats

2006 ◽  
Vol 290 (2) ◽  
pp. E207-E212 ◽  
Author(s):  
Adil El Midaoui ◽  
Jean Louis Chiasson ◽  
Gilles Tancrède ◽  
André Nadeau
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Plasma Concentration ◽  
Free Fatty Acid ◽  
Physical Training ◽  
Ketone Body ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Hydroxybutyric Acid ◽  
Increased Activity

This study was designed to examine whether the training-induced improvement in the plasma concentration of ketone bodies in experimental diabetes mellitus could be explained by changes in the activity of the hepatic ketone body synthesis pathway and/or the plasma free fatty acid levels. Diabetes mellitus was induced by an intravenous injection of streptozotocin (50 mg/kg), and training was carried out on a treadmill. The plasma concentration of β-hydroxybutyric acid was increased ( P < 0.001) in sedentary diabetic rats, and this was partly reversed by training ( P < 0.001). The plasma concentration of free fatty acids was increased ( P < 0.001) in sedentary diabetic rats, and this was reversed to normal by training ( P < 0.001). Diabetes was also associated with an increased activity of the hepatic ketone body synthesis pathway. When the data are expressed as per total liver, physical training decreased the activity of the hepatic ketone body synthesis pathway by 18% in nondiabetic rats ( P < 0.05) and by 22% in diabetic rats ( P < 0.01), the activity present in trained diabetic rats being not statistically different from that of sedentary control rats. These data suggest that the beneficial effects of physical training on the plasma β-hydroxybutyric acid levels in the diabetic state are probably explained in part by a decrease in the activity of the hepatic ketone body synthesis pathway and in part by a decrease in plasma free fatty acid levels.

scholarly journals 3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle

1976 ◽  
Vol 158 (2) ◽  
pp. 509-512 ◽  
Author(s):  
A Fenselau ◽  
K Wallis
Keyword(s):  
Skeletal Muscle ◽  
Coenzyme A ◽  
Substrate Inhibition ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Functional Parameters ◽  
Rat Muscle ◽  
Coa Transferase ◽  
Normal Rat ◽  
Streptozotocin Diabetic Rats

The amounts of succinyl-CoA--3-oxo acid CoA-transferase (EC 2.8.3.5) decrease progressively in skeletal muscle in streptozotocin-diabetic rats, reaching after 10 days about 50% of the value in normal rat muscle. Electrofocusing studies indicate the occurrence of partial proteolysis of the enzyme in diabetic muscle. However, several functional parameters relating to acetoacetate utilization, including substrate inhibition, are quite similar for muscle transferase preparations from normal and diseased rats. The development of pathological ketoacidosis is discussed in the light of these observations.

scholarly journals Cloning of rat brain succinyl-CoA:3-oxoacid CoA-transferase cDNA. Regulation of the mRNA in different rat tissues and during brain development

1987 ◽  
Vol 248 (3) ◽  
pp. 853-857 ◽  
Author(s):  
M K Ganapathi ◽  
M Kwon ◽  
P M Haney ◽  
C McTiernan ◽  
A A Javed ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Rat Brain ◽  
Ketone Bodies ◽  
Rat Kidney ◽  
Relative Rate ◽  
Cdna Clones ◽  
Rat Tissues ◽  
Transferase Activity ◽  
Coa Transferase ◽  
Old Rats

3-Oxoacid CoA-transferase, which catalyses the first committed step in the oxidation of ketone bodies, is uniquely regulated in developing rat brain. Changes in 3-oxoacid CoA-transferase activity in rat brain during the postnatal period are due to changes in the relative rate of synthesis of the enzyme. To study the regulation of this enzyme, we identified, with a specific polyclonal rabbit anti-(rat 3-oxoacid CoA-transferase), two positive cDNA clones (approx. 800 bp) in a lambda gtll expression library, constructed from poly(A)+ RNA from brains of 12-day-old rats. One of these clones (lambda CoA3) was subcloned into M13mp18 and subjected to further characterization. Labelled single-stranded probes prepared by primer extension of the M13mp18 recombinant hybridized to a 3.6 kb mRNA. Rat brain mRNA enriched by polysome immunoadsorption for a single protein of size 60 kDa which corresponds to the precursor form of 3-oxoacid CoA-transferase was also found to be similarly enriched for the hybridizable 3.6 kb mRNA complementary to lambda CoA3. Affinity-selected antibody to the lambda CoA3 fusion protein inhibited 3-oxoacid CoA-transferase activity present in rat brain mitochondrial extracts. The 3.6 kb mRNA for 3-oxoacid CoA-transferase was present in relative abundance in rat kidney and heart, to a lesser extent in suckling brain and mammary gland and negligible in the liver. The specific mRNA was also found to be 3-fold more abundant in the brain from 12-day-old rats as compared with 18-day-old foetuses and adult rats, corresponding to the enzyme activity and relative rate of synthesis profile during development. These data suggest that 3-oxoacid CoA-transferase enzyme activity is regulated at a pretranslational level.

scholarly journals A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

2017 ◽  
Vol 9 (1) ◽  
pp. 31-40
Author(s):  
Juraiporn Somboonwong ◽  
Khunkhong Huchaiyaphum ◽  
Onanong Kulaputana ◽  
Phisit Prapunwattana
Keyword(s):  
Exercise Training ◽  
Ketone Body ◽  
Glycated Hemoglobin ◽  
Ketone Bodies ◽  
Transferase Activity ◽  
Nonesterified Fatty Acids ◽  
Regular Diet ◽  
Coa Transferase ◽  
Ketone Body Metabolism ◽  
Mufa Diet

Abstract Background Monounsaturated fat (MUFA) also has glucose-lowering action, but its effect on ketone bodies is unknown. Objectives To examine the effects of high-MUFA diet alone or in combination with exercise training, which can improve glucose and ketone body metabolism, in a rat model of diabetes. Methods Wistar rats were administered streptozotocin to induce diabetes and then randomly divided into five groups: sedentary rats fed a regular diet (1), a high-saturated-fat diet (2), a high-MUFA diet (3); and exercisetrained rats fed a regular diet (4), and a high-MUFA diet (5). Training was by a treadmill twice daily, 5 days/week. At 12 weeks, glucose, glycated hemoglobin (HbA1c), insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate levels were measured in cardiac blood. Activity of the overall ketone synthesis pathway was determined in liver and 3-ketoacyl-CoA transferase activity determined in gastrocnemius muscle. Results A high-MUFA diet tended to lower plasma glucose without affecting other biochemical variables. Training did not change glucose metabolism, but significantly reduced serum NEFA. Only the high-MUFA diet plus training significantly decreased HbA1c levels. Hepatic ketone synthesis was decreased and 3-ketoacyl-CoA transferase activity was increased by training alone or in combination with a high-MUFA diet. Changes in NEFA, β-hydroxybutyrate, and the enzymatic activities in response to training plus a high-MUFA diet were comparable to those caused by training alone. Conclusion A high-MUFA diet alone does not alter ketone body metabolism. Combination of a MUFA-rich diet and exercise training is more effective than either MUFA or exercise alone for lowering HbA1c.

scholarly journals Beneficial effects of dietary restriction in type 2 diabetic rats: the role of adipokines on inflammation and insulin resistance

2010 ◽  
Vol 104 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Joana Crisóstomo ◽  
Lisa Rodrigues ◽  
Paulo Matafome ◽  
Carmen Amaral ◽  
Elsa Nunes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Dietary Restriction ◽  
Insulin Signalling ◽  
Diabetic Rats ◽  
Energy Restriction ◽  
Beneficial Effects

Inflammation plays an important role in diabetes mellitus and its complications. In this context, the negative cross-talk between adipose tissue and skeletal muscle leads to disturbances in muscle cell insulin signalling and induces insulin resistance. Because several studies have shown that energy restriction brings some benefits to diabetes, the aim of the present study was to evaluate the effects of dietary restriction on systemic and skeletal muscle inflammatory biomarkers, such C-reactive protein, adipokines and cytokines, and in insulin resistance in Goto-Kakizaki rats. This is an animal model of spontaneous non-obese type 2 diabetes with strongly insulin resistance and without dyslipidaemia. Animals were maintained during 2 months of dietary restriction (50 %) and were killed at 6 months of age. Some biochemical determinations were done using ELISA and Western blot. Data from the present study demonstrate that in Goto-Kakizaki rats the dietary restriction improved insulin resistance, NEFA levels and adipokine profile and ameliorated inflammatory cytokines in skeletal muscle. These results indicate that dietary restriction in type 2 diabetes enhances adipose tissue metabolism leading to an improved skeletal muscle insulin sensitivity.

Possible mechanisms responsible for the rise in plasma vasopressin associated with diabetic ketoacidosis in the rat

1988 ◽  
Vol 116 (3) ◽  
pp. 343-348 ◽  
Author(s):  
J. A. Charlton ◽  
C. J. Thompson ◽  
P. H. Baylis
Keyword(s):  
Plasma Concentration ◽  
Diabetic Ketoacidosis ◽  
Ketone Bodies ◽  
Cuff Pressure ◽  
Plasma Osmolality ◽  
Diabetic Rats ◽  
Haemodynamic Changes ◽  
Arterial Pulsation ◽  
Arterial Inflow ◽  
Normal Controls

ABSTRACT The plasma concentration of arginine vasopressin (AVP) is increased in diabetic ketoacidosis (DKA) in man and the rat. Although haemodynamic changes and nausea/emesis may account for the increased secretion of AVP in severe human DKA, they appear not to be responsible in moderate DKA. Streptozotocin-treated rats were studied to investigate other factors possibly involved in the secretion of AVP in DKA. Wistar rats were injected i.p. with streptozotocin (150 mg/kg body weight). Diabetic rats were maintained on 3–4 units protamine–zinc insulin (PZI)/day for 11 days, after which PZI was withdrawn for 3 days in half the rats. The plasma concentration of AVP was greater in rats with DKA than in normal controls (mean 11·4 pmol/l compared with 1·6 pmol/l; P <0·05). Rats with DKA had higher plasma osmolality and concentrations of blood glucose, β-hydroxybutyrate and acetoacetate, but lower plasma carbon dioxide content than diabetic and normal controls (P <0·05). There were no differences in plasma levels of sodium, urea or haematocrit between rats with DKA and controls. In a separate study involving the same procedures, daily systolic blood pressure was measured using a tail cuff to occlude arterial inflow to the tail, and subsequent detection of the cuff pressure at which the first arterial pulsation appeared. No significant differences were detected between normal and diabetic rats and rats with DKA. Exponential relationships between plasma osmolality and plasma AVP (correlation coefficient, r = +0·75; P <0·01), and plasma ketone bodies and plasma AVP (r= +0·60; P <0·05) were obtained. The increase in plasma AVP in the DKA group was not due to haemodynamic changes or nausea/emesis. The results suggest that in early DKA in the rat, increases in the plasma concentration of AVP are related to the metabolic consequences of insulin deficiency and not to hypovolaemia or hypotension. J. Endocr. (1988) 116, 343–348

scholarly journals Gene expression of PPARγ and PGC-1α in human omental and subcutaneous adipose tissues is related to insulin resistance markers and mediates beneficial effects of physical training

2010 ◽  
Vol 162 (3) ◽  
pp. 515-523 ◽  
Author(s):  
Karen Ruschke ◽  
Lauren Fishbein ◽  
Arne Dietrich ◽  
Nora Klöting ◽  
Anke Tönjes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Mrna Expression ◽  
Physical Training ◽  
Adipose Tissues ◽  
Beneficial Effects ◽  
Fat Depots

ObjectiveObesity and type 2 diabetes (T2D) are reaching epidemic proportions in Western societies, and they contribute to substantial morbidity and mortality. The peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) system plays an important role in the regulation of efficient energy utilization and oxidative phosphorylation, both of which are decreased in obesity and insulin resistance.Design and methodsWe measured the metabolic parameters and the expression of PPARγ and PGC-1α mRNA using quantitative real-time PCR in omental and subcutaneous (SC) adipose tissues in an observational study of 153 individuals as well as in SC fat and skeletal muscle in an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and T2D) before and after intensive physical training for 4 weeks.ResultsPPARγ and PGC-1α mRNA expression in both fat depots as well as in skeletal muscle is associated with markers of insulin resistance and cardiovascular risk. PGC-1α mRNA expression is significantly higher in SC fat than in omental fat, whereas PPARγ mRNA expression is not significantly different between these fat depots. Skeletal muscle and SC fat PPARγ and PGC-1α mRNA expression increased significantly in response to physical training.ConclusionsGene expression of PPARγ and PGC-1α in human adipose tissue is related to markers of insulin resistance and cardiovascular risk. Increased muscle and adipose tissue PPARγ and PGC-1α expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.

scholarly journals Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition

1976 ◽  
Vol 158 (2) ◽  
pp. 191-202 ◽  
Author(s):  
M Berger ◽  
S A Hagg ◽  
M N Goodman ◽  
N B Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Lactate Oxidation ◽  
Fed State ◽  
Lactate Release ◽  
Sciatic Nerve Stimulation

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44 mumol/min per 30 g muscle in fed rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35 mumol/min per 30 g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled O2 consumption (from approximately 8 to approximately 25 mumol/min per 30 g of muscle) and increased the release and oxidation of lactate five- to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent; however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter of a fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muslce; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither that neither glycolysis nor the capacity for glucose transport are inhbitied in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidation is inhibited, suggesting diminished activity of pyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.

scholarly journals Effect of Physical Training on the Activity of the Low Km Phosphodiesterase in Heart Ventricular and Skeletal Muscle Tissues of Normal and Diabetic Rats

2020 ◽  
Vol 1 (2) ◽  
pp. 119-126
Author(s):  
Gilles Plourde ◽  
André Nadeau
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Physical Training ◽  
Plasma Insulin ◽  
Diabetic Rats ◽  
Treadmill Running ◽  
Insulin Levels ◽  
Sd Rats ◽  
Muscle Tissues ◽  
Plasma Insulin Levels

This study assessed the effect of physical training on the low Michaelis constant cyclic AMP phosphodiesterase (low Km PDE) activity in heart ventricular tissue and three different skeletal muscle tissues of normal and diabetic rats. Rats were rendered diabetic with streptozotocin (45 mg/kg i.v.) and either kept sedentary (SD, n=16) or submitted to a progressive 10-week treadmill running program (TD, n=17). Two groups of nondiabetic rats served as trained (TC, n=17) and sedentary controls (SC, n=15). The activity of NAD-linked isocitrate dehydrogenase was significantly increased (p < 0.001) in the gastrocnemius muscle of trained animals, confirming that they were adequately trained. Plasma glucose levels were elevated in SD rats (18.8 ± 1.7 mmol/l) compared to those in SC rats (7.7 ± 0.2 mmol/l ; mean ± standard error of the mean [SEM], p < 0.001). These levels were partially normalized following training (12.7 ± 1.7 pmol/l; p < 0.01 vs. SD rats). Plasma insulin levels were significantly reduced in TC rats (223 ± 16 pmol/l) compared with those in SC rats (306 ± 13 pmol/l; p < 0.01). Similarly, the levels in SC rats were significantly different when compared with SD rats (155 ± 15 pmol/l; p < 0.01). In TD rats, plasma insulin levels (156 ± 14 pmol/l) were similar to those of SD rats. This suggests that mild diabetes mellitus in the rat can be improved by endurance training and that improved glycemic control may be mediated by an increase in insulin sensitivity. The low Km PDE activity in the membranes prepared from the four different muscle tissues was not modified by diabetes. Similarly, physical training in normal and diabetic rats did not induce any significant changes in the low Km PDE activity in any of the tissues tested. This suggests that improvements in myocardial contractile function and in glucose homeostasis, as seen in diabetic rats submitted to endurance training, are not associated with changes in PDE.

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