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

The metabolism of coenzyme A and control of its synthesis are reviewed. Pantothenate kinase is an important rate-controlling enzyme in the synthetic pathway of all tissues studied and appears to catalyze the flux-generating reaction of the pathway in cardiac muscle. This enzyme is strongly inhibited by coenzyme A and all of its acyl esters. The cytosolic concentrations of coenzyme A and acetyl coenzyme A in both liver and heart are high enough to totally inhibit pantothenate kinase under all conditions. Free carnitine, but not acetyl carnitine, deinhibits the coenzyme A-inhibited enzyme. Carnitine alone does not increase enzyme activity. Thus changes in the acetyl carnitine-to-carnitine ratio that occur with nutritional states provides a mechanism for regulation of coenzyme A synthetic rates. Changes in the rate of coenzyme A synthesis in liver and heart occurs with fasting, refeeding, and diabetes and in heart muscle with hypertrophy. The pathway and regulation of coenzyme A degradation are not understood.
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PMID:Coenzyme A metabolism. 298 78

The cardiac muscle of BB Wistar rats suffering from diabetes for 8 and 16 weeks (8-Wk and 16-Wk of DM) were examined by light and electron microscopy. The diabetic rats were kept alive by injections of small doses of insulin and exhibited severe hyperglycaemia, glycosuria and weight loss. The heart/body weight ratio of all diabetic groups was greater than that of age matched controls. Over the experimental period, the left ventricular myocardium of the diabetic BB rats sustained damage that was progressively more serious with the duration of the diabetic state. In BB rats after 8-wk of diabetes the myocardium contained large numbers of lipid droplets and glycogen granules around mitochondria which showed patchy swelling, and slight loss of myofilaments. Disruption of mitochondrial membranes and extensive loss of myofilaments were seen in rats diabetic for 16 wk. In addition, dilatation of the sarcoplasmic reticulum-transverse tubular system, formation of a contraction band and myelin bodies and widening of the intercellular space at the fasciae adherens of the intercalated disc were characteristically observed in BB rats after 16-wk of diabetes. However, there were no evident alterations in the capillaries of any diabetic BB rats. Morphometric analyses showed the volume percentage of myofibrils in diabetic rats to be significantly decreased when compared with controls. The loss of myofibrillar elements may be a primary damage induced by insulin deficiency. The formation of contraction bands suggests Ca2+ overload caused by diabetic metabolic disturbances.
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PMID:Ultrastructural alterations in cardiac muscle of diabetic BB Wistar rats. 310 8

The influence of streptozotocin-induced diabetes has been studied on rabbit isolated cardiac muscle responses to noradrenaline and calcium. Seven weeks after treatment with streptozotocin (70 mg/kg i.v.), right atrial contractile rate was found to be depressed, whereas left ventricular papillary muscle function was markedly enhanced. Neither the atrial nor the ventricular (papillary) muscle strip exhibited a remarkable alteration in sensitivity to noradrenaline. Although sensitivity to calcium was not altered in the atrial muscle, papillary muscle strips obtained from diabetic rabbits were supersensitive to calcium. These results suggest that in diabetic animals, right atrial pacemaker function is depressed, while ventricular muscle activity is enhanced. In the diabetic state, this enhanced ventricular muscle function is likely to be associated with an alteration in calcium utilization.
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PMID:The influence of streptozotocin-induced diabetes on myocardial contractile performance in vitro. 401 Mar 84

Biopsy specimens from the myocardium were examined in a series of 145 patients who had elected coronary arterial bypass grafting. The patients were divided into three groups; 1) overtly diabetic (OD) patients; 2) chemically diabetic (CD) patients, who demonstrated impaired glucose tolerance only when stressed with a sugar load; and 3) normoglycemic, nondiabetic (ND) patients, who served as a control group. Tissue plugs from the left anterior apical segment of the heart and from the quadriceps femoris in 71 patients, for comparative evaluation, were prepared for ultrastructural examination. Findings were as follows: 1) Myocardial hypertrophy and interstitial fibrosis were twin characteristic abnormalities, seen in all but two of the biopsy specimens; capillary endothelial changes, the third most common abnormality, were present in approximately half of these specimens, regardless of the patients' metabolic status. 2) In patients matched by sex, age, weight, blood pressure, preoperative myocardial ventricular function, and coronary arterial integrity, capillary basal laminar thickening represented a pathomorphologic hallmark, distinguishing structural alterations in the diabetic from those in the normoglycemic patient. 3) Although clear-cut and statistically significant thickening of basal laminae was noticeable in OD patients, a) in the quadriceps markedly increased laminar thickening was present in a number of ND patients, rendering interpretation of this change in skeletal muscle as pathognomonic for diabetes doubtful; and b) within cardiac muscle this increase in laminar width was less than that seen in skeletal muscle, leaving the functional implications of this alteration in doubt. 4) Early but statistically significant increases in capillary basal laminar thickening were observed in the myocardium of CD patients; these patients demonstrated impaired glucose tolerance only when stressed with a sugar load, without exhibiting overt diabetic manifestations. 5) In this group of highly selected patients with epicardial coronary arterial disease, the histopathologic profile of the diabetic myocardium did not include distinctive abnormalities sufficient to warrant the designation of "diabetic cardiomyopathy," indicating that coronary arterial bypass grafting can be recommended for the diabetic patient who requires this procedure.
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PMID:Pathomorphologic aspects of muscular tissue in diabetes mellitus. 623 97

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.
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PMID:Altered sensitivity of chronic diabetic rat heart to calcium. 636 27

Calcium-tolerant myocytes from the adult rat heart were used to study the effects of EDTA on insulin binding and insulin action. Treatment of cardiocytes with EDTA resulted in a 60% inhibition of insulin binding. This effect was partially reversible by subsequent addition of calcium or magnesium. Scatchard analysis of equilibrium binding data in the presence of calcium and magnesium showed a curvilinear plot with a high-affinity segment having a Kd of 5.7 X 10(-10) mol/L. In the presence of EDTA a linear Scatchard plot was observed with a Kd of 5.6 X 10(-9) mol/L. The total number of insulin receptors remained unaltered under these conditions. In contrast to insulin binding, insulin internalization was not affected by EDTA treatment. Insulin action was studied by measuring the effect of the hormone on the transport of 3-O-methylglucose. Half-maximal action occurred at an insulin concentration of 3 X 10(-10) mol/L and 10(-8) mol/L in control and EDTA-treated cells, respectively. Maximal transport stimulation, however, was not significantly different in both groups (130% and 106%, respectively). In conclusion, low-affinity insulin receptors in cardiac myocytes mediate a biologic response comparable to that of high-affinity sites; moreover, they may be involved in the process of internalization in this tissue. The data suggest a functional role of low-affinity insulin receptors in cardiac muscle.
Diabetes 1984 Mar
PMID:Effect of EDTA on insulin binding and insulin action in isolated cardiocytes from adult rat. Evidence for a functional role of low-affinity insulin receptors. 642 41

An RIA has been developed for rabbit muscle PFK, an allosteric enzyme which catalyzes the pacemaker reaction of glucose utilization. The assay which could accurately measure as little as 12 ng (37.5 fmol) of the tetrameric enzyme was applied to extracts of skeletal and cardiac muscle of animals subjected to four different nutritional conditions and to alloxan diabetes. The concentration of enzyme remained unchanged in all conditions: mean value in anterior tibial muscle was 2.99 microM (S.D., 0.20; N, 32); in left ventricle, 0.66 microM (S.D., 0.07; N, 29). It may be concluded that control of the reaction is mainly, if not exclusively, by allosteric phenomena and not by insulin- or nutrition-dependent changes in intracellular concentration of the enzyme.
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PMID:Intracellular concentration of skeletal and cardiac muscle phosphofructokinase in diabetic and normal animals. 644 31

Lipoprotein lipase (LPL) activity was studied in adipose, muscle and lung tissues of post-weanling rats 48 and 96 hours after experimentally induced diabetes by streptozotocin administration. Weight gain was reduced, and blood glucose level increased about 3-4 fold above the control level as an indication of the diabetic state. LPL activity in brown and white adipose tissues decreased in diabetic rats to 10-30% of the control level. In soleus muscle the LPL activity was slightly enhanced 96 hours after the streptozotocin injection. In cardiac muscle the LPL activity was markedly increased already 48 hours after the administration of streptozotocin and the increase remained significant until 96 hours. There was in the pulmonary tissue also an increase of LPL activity of diabetic rats, although this was significant only 96 hours after streptozotocin treatment. The results suggest marked tissue specific variation in the LPL activity. Moreover, tissue responses to experimentally induced diabetes vary. In adipose tissue the decrease in the LPL activity suggests that lipid transport to adipocytes is decreased while an increase in skeletal and cardiac muscles and in lung tissue proposes that their lipid utilization is enhanced.
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PMID:Adipose, muscle and lung tissue lipoprotein lipase activities in young streptozotocin treated rats. 645 Jul 21

Enkephalin-hydrolytic activity was evaluated in cerebral and cardiac tissue of Wistar rats with experimental streptozotocin-induced diabetes by comparison of the degree of amino acid cleavage from leu-enkephalin in vitro. Ninety days after induction of diabetes the enkephalin-hydrolytic activity was elevated in the cerebral tissue but depressed in the cardiac muscle.
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PMID:The enkephalin-hydrolytic activity of cerebral and cardiac muscle tissue in Wistar rats with streptozotocin diabetes. 646 63

Ultrastructural changes in heart muscle due to chronic diabetes subsequent to a single injection of streptozotocin (65 mg/kg body wt, i.v.) were studied in rats. Presence of diabetes was indicated by hyperglycaemia (plasma glucose, control, 120 +/- 7; diabetic, 448 +/- 21 mg/dl) as well as hypo-insulinaemia (plasma insulin, control, 25.6 +/- 5.2; diabetic, 11.2 +/- 0.5 microU/ml). After 8 weeks of diabetes, the hearts were processed for electron microscopic examination. Cardiac muscle cells in diabetic hearts showed condensation of nuclear chromatin and folding of nuclear membranes. Swelling of mitochondria, clearing of mitochondrial matrix and incorporation of lysosomal membranes into mitochondrial matrix was also noted. A marked increase in both lysosomes and lipid droplets was apparent. Focal areas in diabetic hearts showed contracted sarcomeres, myofibrillar degeneration and separation of the intercalated disc. Atherosclerotic plaque formation as well as structural changes in the smooth muscle or endothelial cells in the small arteries, arterioles or capillaries were not seen to accompany the structural changes in the cardiac muscle cells of the diabetic hearts. This study provides strong evidence for the occurrence of primary myocardial disease in streptozotocin-induced chronic diabetes.
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PMID:Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes. 648 39


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