Altered regulation of cardiac glycogen metabolism in spontaneously diabetic rats

1983 ◽  
Vol 245 (4) ◽  
pp. E379-E383 ◽  
Author(s):  
T. B. Miller
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Metabolic Abnormalities ◽  
Insulin Deficiency ◽  
Kinase Activation ◽  
Chemically Induced ◽  
Spontaneously Diabetic Rats ◽  
Perfused Hearts

Isolated perfused hearts from control Bio-Breeding/Worcester (BB/W) rats and spontaneously diabetic BB/W rats were studied to determine whether metabolic abnormalities that are expressed in alloxan-diabetic rats in the regulation of enzymes involved in glycogen metabolism could be observed in this non-chemically induced insulin-deficient rat. Perfusion of hearts from control rats with 10(-8) M insulin for 10 min resulted in activation of glycogen synthase (30% synthase I without insulin to 44% synthase I with insulin). Perfusion of hearts from BB/W diabetic rats demonstrated a lack of acute synthase activation with insulin and a 45% decrease in synthase phosphatase activity. Perfusion of hearts from BB/W diabetic rats with 0.28 microM epinephrine for 1 min resulted in a greater activation of phosphorylase (44% phosphorylase a) than that observed in BB/W control hearts (31% phosphorylase a) perfused under the same conditions. Epinephrine produced similar changes in cyclic AMP accumulation, protein kinase activation, and phosphorylase kinase activation in perfused hearts of BB/W control and diabetic rats. Further, phosphorylase phosphatase activities were not changed by epinephrine or insulin deficiency. These studies further document metabolic abnormalities in the BB/W diabetic rat that are attributable to insulin deficiency in a non-chemically induced model for insulin-dependent diabetes.

scholarly journals The effect of streptozotocin-induced diabetes and of insulin supplementation on glycogen metabolism in rat liver

1977 ◽  
Vol 168 (3) ◽  
pp. 541-548 ◽  
Author(s):  
R L Khandelwal ◽  
S M Zinman ◽  
E J Zebrowski
Keyword(s):  
Phosphatase Activity ◽  
Insulin Treatment ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Diabetic Rats ◽  
Phosphorylase Kinase ◽  
Metabolizing Enzymes ◽  
Heat Stable ◽  
Heat Stable Protein ◽  
Streptozotocin Induced Diabetes

The effects of streptozotocin-induced diabetes and of insulin supplementation to diabetic rats on glycogen-metabolizing enzymes in liver were determined. The results were compared with those from control animals. The activities of glycogenolytic enzymes, i.e. phosphorylase (both a and b), phosphorylase kinase and protein kinase (in the presence or in the absence of cyclic AMP), were significantly decreased in the diabetic animals. The enzyme activities were restored to control values by insulin therapy. Glycogen synthase (I-form) activity, similarly decreased in the diabetic animals, was also restored to control values after the administration of insulin. The increase in glycogen synthase(I-form) activity after insulin treatment was associated with a concomitant increase in phosphoprotein phosphatase activity. The increase in phosphatase activity was due to (i) a change in the activity of the enzyme itself and (ii) a decrease in a heat stable protein inhibitor of the phosphatase activity.

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.

In vivo and in vitro resistance to maximal insulin-stimulated glucose disposal in insulin deficiency

1985 ◽  
Vol 249 (3) ◽  
pp. E312-E316 ◽  
Author(s):  
E. Dall'Aglio ◽  
H. Chang ◽  
C. B. Hollenbeck ◽  
C. E. Mondon ◽  
C. Sims ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Diabetic Rat ◽  
Insulin Deficiency ◽  
Fat Cell ◽  
Total Body

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.

Myocardial lipoprotein lipase activity: regulation by diabetes and fructose-induced hypertriglyceridemia

1995 ◽  
Vol 73 (3) ◽  
pp. 369-377 ◽  
Author(s):  
Limin Liu ◽  
David L. Severson
Keyword(s):  
Lipoprotein Lipase ◽  
Selective Reduction ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Compensatory Response ◽  
Perfusion Solution ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Control Plasma ◽  
Sustained Increase

The decrease in myocardial lipoprotein lipase (LPL) activity observed previously in acute, severe models of insulin-deficient diabetes may be a compensatory response to hypertriglyceridemia and a sustained increase in fatty acid delivery to cardiomyocytes. The administration of fructose (10% solution in the drinking water for 4 days) to rats produced hypertriglyceridemia, but heparin-releasable LPL activity from perfused hearts and total and heparin-releasable LPL activities in isolated cardiomyocytes were not reduced. The acute (4 day) induction of a mild diabetic state (60 mg/kg streptozotocin) resulted in modest hypertriglyceridemia, and a selective decrease in heparin-releasable LPL activity in perfused hearts; LPL activity in cardiomyocytes from diabetic rat hearts was not reduced. Therefore, the diabetes-induced fall in myocardial LPL activity is not secondary to hypertriglyceridemia, since fructose treatment did not change LPL activity. Perfusion of rat hearts with 100 μM lysophosphatidylcholine (LPC) released a small amount of LPL activity into the perfusate, but only if albumin was omitted from the perfusion solution. Thus, the selective reduction in heparin-releasable LPL activity in perfused diabetic hearts is probably not the consequence of displacement by LPC, a lipolytic product of the LPL-catalyzed degradation of triacylglycerol-rich lipoproteins. Circulating LPL activity in the plasma of diabetic rats was not decreased relative to control plasma enzyme activity; therefore, the reduction in heparin-releasable LPL activity is not because circulating LPL was less available for uptake by the endothelium in diabetic hearts.Key words: diabetes, lipoprotein lipase, perfused hearts, cardiomyocytes.

scholarly journals Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats

1999 ◽  
Vol 162 (2) ◽  
pp. 251-258 ◽  
Author(s):  
J Verhaeghe ◽  
R van Bree ◽  
E van Herck ◽  
I Jans ◽  
Z Zaman ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Diabetic Rats ◽  
The Novel ◽  
Insulin Deficiency ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Spontaneously Diabetic Rats ◽  
And Control

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) concentrations have been found to be decreased in diabetic humans and rats. To investigate further the regulation of plasma Ca in diabetes, first we measured Ca(2+), P, Mg, parathyroid hormone(1-34) (PTH), and total and free 1,25(OH)(2)D(3) in male spontaneously diabetic rats 7 and 28 days after the onset of glycosuria. Secondly, we studied changes in the levels of PTH and 1,25(OH)(2)D(3) in response to hypocalcaemia induced by an i.v. infusion of EGTA (2.5%, wt/vol.) for 24 h, and changes in the levels of 1,25(OH)(2)D(3) in response to an i.v. infusion of rat PTH (10 microgram over 24 h) without or with concomitant EGTA infusion (producing hypercalcaemia or normo/hypocalcaemia respectively), in diabetic and control rats. Ca(2+), P, Mg and PTH concentrations remained within the control ranges after 7 and 28 days of glycosuria; 1,25(OH)(2)D(3) concentrations were decreased after 7, but not after 28, days of glycosuria. PTH concentrations showed a similar rise during EGTA-induced hypocalcaemia in control and diabetic rats compared with saline-infused rats, whereas 1,25(OH)(2)D(3) concentrations were unchanged in both groups. Total and free 1,25(OH)(2)D(3) levels were comparably (about 3-fold) increased during PTH, but not during combined PTH and EGTA infusion in control and diabetic rats. Total 1, 25(OH)(2)D(3) concentrations were lower in the diabetic groups infused with saline or PTH than in their respective controls, and there was a similar trend in the PTH+EGTA-infused group; free 1, 25(OH)(2)D(3) levels, however, were normal or increased in the diabetic groups, confirming our previous data. The novel finding of this study is that, despite severe insulin deficiency and altered 1, 25(OH)(2)D(3) levels, the in vivo response of PTH levels to hypocalcaemia and the in vivo response of 1,25(OH)(2)D(3) levels to PTH in diabetic rats are comparable with those found in nondiabetic rats.

Opposite effects of hyperglycemia and insulin deficiency on liver glycogen synthase phosphatase activity in the diabetic rat

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 363-366 ◽  
Author(s):  
L. Lavoie ◽  
D. Dimitrakoudis ◽  
A. Marette ◽  
B. Annabi ◽  
A. Klip ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Glycogen Synthase ◽  
Liver Glycogen ◽  
Diabetic Rat ◽  
Insulin Deficiency

Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy

1983 ◽  
Vol 244 (6) ◽  
pp. E528-E535 ◽  
Author(s):  
P. K. Ganguly ◽  
G. N. Pierce ◽  
K. S. Dhalla ◽  
N. S. Dhalla
Keyword(s):  
Thyroid Hormone ◽  
Calcium Transport ◽  
Protein Composition ◽  
Hormone Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Deficiency ◽  
Glucose Levels ◽  
Streptozotocin Induced Diabetes ◽  
Rat Thyroid

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.

Opposite Effects of Hyperglycemia and Insulin Deficiency on Liver Glycogen Synthase Phosphatase Activity in the Diabetic Rat

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 363-366 ◽  
Author(s):  
L. Lavoie ◽  
D. Dimitrakoudis ◽  
A. Marette ◽  
B. Annabi ◽  
A. Klip ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Glycogen Synthase ◽  
Liver Glycogen ◽  
Diabetic Rat ◽  
Insulin Deficiency

Transient ischemia induces regional myocardial glycogen synthase activation and glycogen synthesis in vivo

1995 ◽  
Vol 268 (1) ◽  
pp. H364-H370 ◽  
Author(s):  
P. H. McNulty ◽  
M. C. Luba
Keyword(s):  
Coronary Artery ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Diabetic Rats ◽  
Synthesis Rate ◽  
Transient Ischemia

Glycogen is consumed during ischemic preconditioning and synthesized during the subsequent period of ischemic tolerance. To better understand this sequence, we examined the effect of brief coronary artery occlusions on regional myocardial glycogen metabolism in intact, anesthetized rats. Sequential 2-min periods of left coronary artery occlusion reduced the glycogen concentration of the anterior left ventricle approximately 30% relative to the posterior region. During subsequent reperfusion, the activity of the physiologically active glycogen synthase I form of glycogen synthase increased threefold in the anterior region (0.58 +/- 0.11 vs. 0.18 +/- 0.08 mumol.g-1.min-1, P < 0.01), stimulating a similar regional increase in glycogen synthesis rate (0.24 +/- 0.04 vs. 0.08 +/- 0.03 mumol.g-1.min-1, P < 0.01). These events were preceded by a rise in regional glucose 6-phosphate concentration, which increased the activity of a myocardial glycogen synthase phosphatase. In diabetic rats glycogen synthase phosphatase activity was significantly lower, and postischemic glycogen synthase activation was significantly impaired. These data suggest the operation of a feedback loop in which transient ischemia leads to a glucose 6-phosphate-mediated increase in the activity of a phosphoprotein phosphatase active toward glycogen synthase. This suggests phospho-protein phosphatase activation may be a feature of the preconditioned myocardium.

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