Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hearts isolated from non-insulin-dependent diabetic rats were found to exhibit reduced rates of basal and insulin-stimulated glucose metabolism. Since tissue levels of fructose 1,6-bisphosphate are significantly reduced in the diabetic heart, it was concluded that phosphofructokinase may be inhibited. However, neither glycogen nor glucose 6-phosphate accumulated in the myocyte, indicating that the phosphofructokinase reaction was not a bottleneck diverting substrate away from glycolysis. The other major factor contributing to decreased glycolytic flux in the diabetic heart is the impairment in glucose transport. Both basal and insulin-stimulated transport of 3-O-methyl-D-glucose was 30% less in the diabetic heart. While insulin sensitivity was unaltered in the diabetic rat, insulin responsiveness was decreased, indicating that the impairment in insulin-stimulated hexose transport was caused by a post-receptor defect. The net result of these abnormalities in glucose metabolism is a significant reduction in the rate of ATP synthesis by the diabetic heart.
Diabetes 1986 May
PMID:Postreceptor myocardial metabolic defect in a rat model of non-insulin-dependent diabetes mellitus. 293 76

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.
 ...
PMID:Cardiac function in spontaneously hypertensive diabetic rats. 294 94

Wistar rats were injected with streptozotocin (SZ) at 3 days of age. This maneuver produced a marked glucose intolerance, as determined by intraperitoneal glucose tolerance tests, but plasma fasting and nonfasting glucose values remained at or near normal throughout the 12-mo study period. Hearts obtained from these glucose-intolerant rats exhibited a progressive cardiomyopathy that consisted of both contractile and metabolic abnormalities. Contractile abnormalities were characterized by reductions in aortic output, ventricular pressure, and cardiac work. Associated with these mechanical defects was a decrease in glucose utilization. These abnormalities were not ameliorated by acute exposure to insulin or changes in the work load of the heart. These results demonstrate that, in the rat, a progressive cardiomyopathy results from persistent glucose intolerance in the absence of fasting hyperglycemia. This cardiomyopathy is reminiscent of that described in human noninsulin-dependent diabetes.
 ...
PMID:Development of a cardiomyopathy in a model of noninsulin-dependent diabetes. 315 19

Myocardial fatty acid metabolism was studied in spontaneously-diabetic "BB" Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of "BB" Wistar rats, insulin-treated diabetic "BB" rats, and diabetic "BB" rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (1-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 +/- 0.043 and 0.528 +/- 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 +/- 0.032 and 0.629 +/- 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals was accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 +/- 0.3 mumol/g dry wt/30 min versus 4.8 +/- 0.3, 5.9 +/- 0.7, and 5.7 +/- 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 +/- 25 nmol/g dry wt versus 484 +/- 27, 508 +/- 56, and 534 +/- 9, in treated diabetic, nondiabetic, and control rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Metabolism of palmitate in isolated working hearts from spontaneously diabetic "BB" Wistar rats. 331 91

Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-maximal relaxation (RT1/2), and positive and negative dP/dt were measured during generation of left ventricular filling curves before and after 90 minutes of low-flow ischemia. Hearts from diabetic rabbits (blood glucose, 384 +/- 28 mg/dl, mean +/- 95% confidence limits) had left ventricular developed and diastolic pressures similar to normal hearts but exhibited significant increases in TTPP and RT1/2 with decreased positive and negative dP/dt. Left ventricular chamber volume relative to heart mass was greater in diabetic than in normal hearts. Recovery of developed pressure after ischemia was similar in normal (41 +/- 16%) and diabetic hearts (47 +/- 13%). In diabetic hearts during recovery from ischemia, TTPP and R1/2 remained increased compared with normal hearts, with positive and negative dP/dt decreased compared with normal hearts, in proportion to the preischemic differences. After ischemia, high-energy phosphates were depleted to the same extent in normal and diabetic rabbits. In coronary ligation experiments, histochemically determined infarct size in diabetic rabbits after 30 minutes occlusion and 24 hours reperfusion was similar to that in normal rabbits when adjusted for a significantly smaller heart weight and a correspondingly smaller anatomic risk region in the diabetic animals. Thus, despite characteristic abnormalities of mechanical function in diabetic hearts, the severity of injury after ischemia with reperfusion was normal for diabetic hearts.
 ...
PMID:Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts. 335 80

The relationship of external work to exogenous substrate supply and whole heart lipid content was studied in hearts isolated from 27 normal and 24 alloxan-diabetic rabbits. In addition, we evaluated hearts from seven rabbits after 4 days of untreated diabetes followed by 10 days of insulin therapy. Hearts were retrogradely perfused with erythrocyte-enriched modified Krebs-Henseleit media in which glucose, palmitate, and insulin were present in concentrations simulating diabetic plasma (13 mM, 0.4 mM, and 15 microU/ml, respectively). Diabetes was associated with a greater than 40% reduction in peak left ventricular systolic pressure, dP/dtmax, and left ventricular pressure-time index (P less than 0.01 for each). Perfusion of hearts from six diabetic animals with low concentrations of exogenous fatty acid (0.06 mM) normalized left ventricular (LV) performance. Insulin therapy also completely normalized LV performance. This improvement was associated with lower heart fatty acid and triacylglycerol content. These studies suggest that the myocardial dysfunction in hearts from rabbits with alloxan-induced diabetes of 2-wk duration may be, in part, due to enhanced sensitivity to deleterious effects of high exogenous levels of fatty acid.
 ...
PMID:Effect of fatty acid on performance and lipid content of hearts from diabetic rabbits. 352 33

Streptozocin-diabetic rats were treated with a combination of triiodothyronine and carnitine for 6 weeks. These compounds were used as they are known to correct the diabetes-induced depression of cardiac myosin ATPase and sarcoplasmic reticular (SR) calcium uptake, respectively. Myocardial performance, which was assessed using the working heart preparation, revealed a depression of function in untreated diabetics when compared with controls at most left atrial filling pressures. Hearts from diabetic rats treated with the combination exhibited depression at only the higher filling pressures as compared with untreated or treated controls. The results suggest that functional alterations occurring as a result of diabetes cannot be accounted for by the depression of cardiac myosin ATPase and SR calcium uptake alone.
 ...
PMID:Effects of triiodothyronine and carnitine therapy on myocardial dysfunction in diabetic rats. 375 16

Altered responsiveness to and metabolism of various eicosanoids in diabetic animals and patients has been reported by several investigators. The purpose of this investigation was to examine the coronary vascular responsiveness of alloxan-diabetic rats to the leukotrienes. Hearts from 12- to 16-week-old alloxan-diabetic rats and weight-matched controls were perfused at constant flow by the Langendorff method. Coronary vasoactivity to leukotrienes B4, C4, D4 and E4 was assessed by measuring the change in coronary perfusion pressure upon infusion of these eicosanoids. Hearts from diabetic rats showed increased responsiveness to leukotrienes C4 (4-40 nM) and D4 (10-100 nM). Both control and diabetic rat hearts were only slightly responsive to leukotriene E4, and no difference between the two groups existed in the reactivity to this leukotriene. Neither group was responsive to the chemotactic leukotriene, B4. Perfusion of the hearts with the cyclooxygenase inhibitor, ibuprofen, failed to alter the coronary vascular responses to the leukotrienes. The coronary constrictor effects of the leukotrienes are the primary effect of these agents on the rat heart, since heart rate does not change significantly, and changes in contractile force are secondary to the coronary vascular constriction. These alterations in responsiveness to leukotrienes may play a role in the cardiovascular complications associated with diabetes.
 ...
PMID:Altered coronary vascular responsiveness to leukotrienes in alloxan-diabetic rats. 632 35

Autonomic neuropathy of the heart associated with a primary vagal dysfunction has been frequently found in chronic diabetic patients. Little is known about the responses of hearts obtained from experimentally induced diabetic animals to cholinergic agonists. We have studied the effects of carbachol on isolated perfused working hearts from alloxan- and streptozotocin-diabetic rats as well as hearts from age-matched controls at various time points after the induction of diabetes. Carbachol produced a dose-dependent (10(-8)-10(-5) or 3 x 10(-5) M) reduction in the basal rate of left ventricular pressure development (+dP/dt) in control and diabetic rat hearts at all of the time points studied. There was no change in the sensitivity of diabetic rat hearts to carbachol until about 30 days after induction of diabetes. Diabetic rat hearts exhibited a reduced sensitivity to carbachol at 100 days after induction compared to age-matched control hearts. Hearts isolated from diabetic rats at 180,240 and 360 days were more sensitive to carbachol compared with control hearts. A general decrease in sensitivity of the heart to carbachol was observed in both control and diabetic rats at 360 days. The results demonstrate that the sensitivity of diabetic myocardium changes as the disease state progresses. The alterations could be due to the development of an autonomic neuropathy in the heart.
 ...
PMID:Effect of alloxan- and streptozotocin-induced diabetes on isolated rat heart responsiveness to carbachol. 634 41

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.
 ...
PMID:Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. 634 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>