Effects of vanadium treatment on the alterations of cardiac glycogen phosphorylase and phosphorylase kinase in streptozotocin-induced chronic diabetic rats

1994 ◽  
Vol 72 (12) ◽  
pp. 1537-1543 ◽  
Author(s):  
Heyi Liu ◽  
John H. McNeill
Keyword(s):  
Rat Heart ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Phosphorylase Kinase ◽  
Beneficial Effects ◽  
Camp Pathway ◽  
Vanadyl Sulphate ◽  
Camp Levels ◽  
Camp Elevation

Supersensitivity to isoproterenol (ISO) induced activation of cardiac phosphorylase in diabetic rat heart has been previously demonstrated and was also reproduced in this study. To explore further the nature of this supersensitivity, we examined the activity of phosphorylase kinase and the level of cyclic AMP (cAMP) in this tissue. We observed a significantly enhanced activation of phosphorylase kinase but no increase in cAMP levels in response to ISO stimulation in diabetic rat heart, suggesting that the supersensitivity of phosphorylase activation in diabetic heart may result from an enhanced activation of phosphorylase kinase that does not involve the cAMP pathway. On the other hand, perfusion of diabetic rat heart with verapamil (5 × 10−8 M) prior to ISO stimulation abolished the enhanced cardiac phosphorylase activation, suggesting a role for calcium in the supersensitivity of phosphorylase activation. Furthermore, treatment of the diabetic rats with an insulin-like compound, vanadyl sulphate, completely abolished the enhanced cardiac phosphorylase activation and restored the increase in ISO-induced cAMP elevation in diabetic heart. The present study has provided further information on the changes of phosphorylase activation in the diabetic rat heart and demonstrated beneficial effects of vanadyl sulphate on the pathway leading to phosphorylase activation in diabetic rat heart.Key words: phosphorylase, phosphorylase kinase, catecholamines, vanadium.

Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy

1983 ◽  
Vol 244 (6) ◽  
pp. H844-H851 ◽  
Author(s):  
R. V. Vadlamudi ◽  
J. H. McNeill
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Phosphorylase Activity ◽  
Camp Content ◽  
Rat Hearts ◽  
Underlying Causes ◽  
Camp Levels ◽  
Working Rat Heart ◽  
Time Point

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.

Metabolism of VLDL is increased in streptozotocin-induced diabetic rat hearts

2000 ◽  
Vol 278 (6) ◽  
pp. H1874-H1882 ◽  
Author(s):  
Nandakumar Sambandam ◽  
Mohammed A. Abrahani ◽  
Scott Craig ◽  
Osama Al-Atar ◽  
Esther Jeon ◽  
...  
Keyword(s):  
Lipolytic Activity ◽  
Isolated Heart ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Rat Hearts ◽  
Heparin Plasma

In streptozotocin (STZ)-induced diabetic rats, we previously showed an increased heparin-releasable (luminal) lipoprotein lipase (LPL) activity from perfused hearts. To study the effect of this enlarged LPL pool on triglyceride (TG)-rich lipoproteins, we examined the metabolism of very-low-density lipoprotein (VLDL) perfused through control and diabetic hearts. Diabetic rats had elevated TG levels compared with control. However, fasting for 16 h abolished this difference. When the plasma lipoprotein fraction of density <1.006 g/ml from fasted control and diabetic rats was incubated in vitro with purified bovine or rat LPL, VLDL from diabetic animals was hydrolyzed as proficiently as VLDL from control animals. Post-heparin plasma lipolytic activity was comparable in control and diabetic animals. However, perfusion of control and diabetic rats with heparinase indicated that diabetic hearts had larger amounts of LPL bound to heparan sulfate proteoglycan-binding sites. [3H]VLDL obtained from control rats, when recirculated through the isolated heart, disappeared at a significantly faster rate from diabetic than from control rat hearts. This increased VLDL-TG hydrolysis was essentially abolished by prior perfusion of the diabetic heart with heparin, implicating LPL in this process. These findings suggest that the enlarged LPL pool in the diabetic heart is present at a functionally relevant location (at the capillary lumen) and is capable of hydrolyzing VLDL. This could increase the delivery of free fatty acid to the heart, and the resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat.

Altered sensitivity of chronic diabetic rat heart to calcium

1983 ◽  
Vol 245 (6) ◽  
pp. E560-E567 ◽  
Author(s):  
D. R. Bielefeld ◽  
C. S. Pace ◽  
B. R. Boshell
Keyword(s):  
Rat Heart ◽  
Calcium Metabolism ◽  
Left Ventricular Pressure ◽  
Calcium Sensitivity ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Isolated Hearts ◽  
Pressure Development

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.

scholarly journals Decrease in cardiac phosphatidylglycerol in streptozotocin-induced diabetic rats does not affect cardiolipin biosynthesis: evidence for distinct pools of phosphatidylglycerol in the heart

1995 ◽  
Vol 306 (3) ◽  
pp. 759-764 ◽  
Author(s):  
G M Hatch ◽  
S G Cao ◽  
A Angel
Keyword(s):  
Rat Heart ◽  
Specific Radioactivity ◽  
Fold Increase ◽  
Mitochondrial Fraction ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Continuous Pulse ◽  
Pool Sizes

Biosynthesis of phosphatidylglycerol (PG) and cardiolipin (CL) were investigated in perfused hearts of diabetic rats 4 days or 28 days after streptozotocin injection. Sham-injected and insulin-treated diabetic rats were used as controls. In addition, another group of rats fasted for 54 h was examined. Isolated rat hearts from these groups were perfused for 30 min with [32P]P(i), and the radioactivity incorporated into PG and CL and their pool sizes were determined in heart ventricles. There was no difference in the amount of radioactivity incorporated into CL, PG or other phospholipids between all groups. In addition, the pool sizes of CL and other phospholipids were unaltered. However, a striking decrease in the pool size of PG was observed in both diabetic and fasted rats compared to sham- and insulin-treated controls at 4 days after streptozotocin injection. The decrease in PG mass in diabetic rats was rapid (within 24-48 h) and was localized to cardiac membranes. Diabetes did not affect the activity of the enzymes of PG and CL biosynthesis in the mitochondrial fraction, or phospholipase A activity in subcellular fractions prepared from rat heart homogenates. In addition, pulse-chase experiments confirmed that diabetes did not affect the rate of new PG or CL biosynthesis. Since radioactivity associated with PG was unaltered in continuous-pulse perfusion experiments, a calculated 1.8-fold increase in the specific radioactivity of cardiac PG was observed in the hearts of acute diabetic rats compared with controls. Since the radioactivity incorporated into PG and CL, and the rate of CL biosynthesis, were unaltered in diabetic-rat hearts compared with controls, new CL was probably synthesized from newly synthesized PG. We postulate the existence of distinct pools of PG in the heart, and that the pool of newly synthesized PG used for CL biosynthesis does not appear to mix immediately with the pre-existing pool of PG in the isolated intact rat heart.

Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis

1998 ◽  
Vol 274 (6) ◽  
pp. E984-E991 ◽  
Author(s):  
Firas Saker ◽  
Juan Ybarra ◽  
Patrick Leahy ◽  
Richard W. Hanson ◽  
Satish C. Kalhan ◽  
...  
Keyword(s):  
Cobalt Chloride ◽  
Glucose Production ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Lowering Effect ◽  
Significant Decrement ◽  
Camp Levels

Results of previous studies indicated that treatment of diabetic rats (induced by streptozotocin) with cobalt chloride (CoCl2) resulted in a significant decrement in serum glucose concentration. The present study was designed to determine the potential role of enhanced glucose uptake vs. decreased glucose production in the above response. The rate of systemic appearance of glucose, measured under fasting conditions using [3-3H]glucose tracer, was reduced from 35.5 ± 2.5 to 17.5 ± 1.8 μmol ⋅ kg−1 ⋅ min−1in diabetic rats treated with 2 mM CoCl2 added to the drinking water for 10–14 days ( P < 0.01). Tissue accumulation of intravenously administered 2-deoxy-[14C]glucose was significantly reduced in kidney and eye of diabetic rats treated with CoCl2, whereas the uptake remained unchanged in several other tissues including cerebrum, red and white skeletal muscle, heart, and liver. The relative content of phospho enolpyruvate carboxykinase (PEPCK) mRNA was increased 3.1-fold in livers of diabetic compared with normal rats ( P < 0.001), and treatment of diabetic rats with CoCl2 decreased hepatic PEPCK mRNA levels to normal. The content of PEPCK mRNA in the liver was decreased by 33% in CoCl2-treated normal rats ( P < 0.05). Treatment with CoCl2 resulted in no change in cAMP levels in the livers of either diabetic or normal rats. These results suggest that the glycemia-lowering effect of CoCl2 is mediated by reductions in the rate of systemic appearance of glucose and hepatic gluconeogenesis.

Effects of prostaglandin E1 in diabetic heart

1983 ◽  
Vol 245 (6) ◽  
pp. H1039-H1042
Author(s):  
T. B. Miller
Keyword(s):  
Protein Kinase ◽  
Calcium Metabolism ◽  
Prostaglandin E1 ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Phosphorylase Kinase ◽  
Camp Accumulation ◽  
Cyclic Monophosphate ◽  
Perfused Hearts

Isolated perfused hearts from normal and alloxan-diabetic rats were studied to determine the effects of prostaglandin E1 (PGE1) on phosphorylase activation in the insulin-deficient state. Perfusion of hearts from normal and diabetic rats with 3 X 10(-5) M PGE1 for the final 2 min resulted in activation to the same extent of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, cAMP-sensitive protein kinase, and phosphorylase kinase. Although phosphorylase activation was somewhat suppressed in both the normal and diabetic heart, PGE1 produced a 36% increase in phosphorylase a in normal hearts and a 44% increase in phosphorylase a in diabetic hearts. The decreased effectiveness of phosphorylase activation by PGE1 appears to be located beyond activation of phosphorylase kinase and perhaps involves an alteration in phosphorylase sensitivity to phosphorylase kinase. Further, the activation of phosphorylase by phosphorylase kinase is hypersensitive in hearts of diabetic rats, perhaps due to a diabetes-related alteration in calcium metabolism.

Beneficial Effects of Selenium on Some Enzymes of Diabetic Rat Heart

2005 ◽  
Vol 103 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Nuriye Nuray Ulusu ◽  
Belma Turan
Keyword(s):  
Rat Heart ◽  
Diabetic Rat ◽  
Beneficial Effects

Contractile Dysfunction in the Diabetic-Rat Heart is An Intrinsic Abnormality of the Cardiac Myocyte

1994 ◽  
Vol 86 (3) ◽  
pp. 257-262 ◽  
Author(s):  
Hideki Okayama ◽  
Mareomi Hamada ◽  
Kunio Hiwada
Keyword(s):  
Time Constant ◽  
Rat Heart ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Cell Length ◽  
Diabetic Rat ◽  
Maximal Velocity ◽  
Resting Cell ◽  
Velocity Of Shortening ◽  
Pressure Fall

1. In order to clarify whether the myocardial dysfunction observed in diabetic-rat hearts is an intrinsic property of the myocytes or not, we investigated cardiac function and myocyte contractile function in diabetic rats 5 weeks after the injection of streptozotocin. 2. Maximal and minimal dP/dt and time constant of isovolumic pressure fall were measured using a micromanometer in diabetic and age-matched control rats. 3. Isolated myocytes were enzymically obtained from each rat heart and were stimulated at 1 Hz (37°C) in a buffer containing 1.5 mmol/l Ca2+. The images of myocyte contractions were recorded by a video system. Normalized maximal velocity of shortening (maximal velocity of cell shortening/resting cell length; s−1), normalized maximal velocity of relengthening (maximal velocity of cell relengthening/resting cell length; s−1) and extent of shortening [(twitch amplitude/resting cell length) × 100;%] were analysed by a digitalized computer as contractile functions of the myocyte. 4. The maximal and minimal dP/dt in diabetic rats (7876, 5341 mmHg/s) were significantly lower than those in control rats (9349, 7876 mmHg/s). The time constant of isovolumic pressure fall in diabetic rats (12.7 ms) was significantly greater than that in control rats (8.6 ms). Moreover, the normalized maximal velocity of shortening, normalized maximal velocity of relengthening and extent of shortening in myocytes from diabetic rats (1.40 s−1, 1.38 s−1, 9.5%) were significantly lower than those in myocytes from control rats (1.64 s−1, 1.60 s−1, 11.8%). 5. These results suggest that contractile impairment in this diabetic-rat heart model is mainly due to an intrinsic abnormality of the cardiac myocytes.

scholarly journals Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chi Xiao ◽  
Man-Li Xia ◽  
Jue Wang ◽  
Xin-Ru Zhou ◽  
Yang-Yun Lou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Isolated Rat Heart ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

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