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)

Previous studies have shown that in rats, diabetes mellitus induces a 45% decrease in cardiac Ca++-activated myosin ATPase activity which is accompanied by a decrease in myosin isoenzyme V1 and an increase in myosin isoenzyme V3 levels. Insulin administration reverts Ca++-activated myosin ATPase activity and myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on Ca++-myosin ATPase activity and myosin isoenzyme distribution are direct effects of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To determine if insulin may exert part of its effects by the latter route, diabetic rats were fed a normal, glucose, or fructose diet. Unlike glucose, fructose can enter the initial steps of the glycolytic pathway in the absence of insulin. Placing diabetic rats on different forms of 60% fructose diets for 4 weeks led to a 20-35% increase in Ca++-activated myosin ATPase activity, which was highly significant (normal Ca++-activated myosin ATPase activity, 0.917 mumol Pi/mg protein X min; diabetic, 0.553 mumol Pi/mg protein X min; diabetic + fructose, 0.661 mumol Pi/mg protein X min). The increase in Ca++-activated myosin ATPase activity was accompanied by increased myosin isoenzyme V1 and decreased myosin isoenzyme V3 levels. Feeding animals a 60% glucose diet did not lead to changes in Ca++-activated myosin ATPase activity or myosin isoenzyme distribution. The fructose-induced increase in Ca++-activated myosin ATPase activity and alteration in myosin isoenzyme distribution occurred in the absence of changes in insulin and thyroid hormone levels or improvement in the general metabolic status of fructose-fed diabetic rats.
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PMID:Fructose feeding increases Ca++-activated myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. 623 27

Diabetes mellitus causes congestive heart failure in humans, independent of atherosclerosis. The present study extends previous work on the reversibility, with insulin, of the alterations in myocardial function and contractile protein biochemistry observed in diabetic rats. The response of these alterations to different fixed doses of insulin was explored. Diabetic rats were given 0, 0.5, 1, 1.5, 2, or 2.5 U of insulin daily for 6 wk. Papillary muscle function, actomyosin ATPase, and myosin isoenzyme distribution showed progressive normalization with increasing insulin dose as blood glucose concentration returned to normal. Thus insulin therapy in diabetic rats on a normal diet produces continuous improvement in cardiac function and biochemistry as euglycemia is approached. This study also suggests that mild diabetes results in qualitatively identical, although quantitatively less pronounced, myocardial changes compared with those observed in severely diabetic rats.
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PMID:Diabetic cardiomyopathy in rats: mechanical and biochemical response to different insulin doses. 623 41

Pancreatic islets contain enzyme activity which catalyzes the phosphorylation by MgATP of cardiac, skeletal, or smooth muscle myosin light chains. The enzyme is activated by calcium (Ka = 10 microM) and calmodulin (Ka = 2 nM) and inhibited by trifluoperazine (Ki = 10 microM), a known inhibitor of calmodulin and of insulin secretion. The enzyme binds to a calmodulin affinity column when Ca2+ is present and is eluted when Ca2+ is omitted. These are the properties of myosin light chain kinase. Since phosphorylation of smooth muscle myosin is necessary for its activation by actin, the kinase may have a key role in coupling stimuli that increase intracellular calcium to the contractile processes involved in insulin secretion.
Diabetes 1982 Jun
PMID:Calcium-calmodulin-dependent myosin phosphorylation by pancreatic islets. 629 60

In order to determine whether diabetic cardiomyopathy in rats is associated with altered contractile proteins, male and female rats were made diabetic with intravenous streptozotocin (STZ). Calcium ATPase activity of cardiac actomyosin was significantly decreased after 1 week of diabetes and was depressed by 60% by 2 weeks. Rats pretreated with 3-O-methyl glucose to prevent the hyperglycemia caused by STZ had normal Ca2+-actomyosin ATPase activities, and non-diabetic rats whose food was restricted to keep their body and heart weights similar to those found in diabetic animals had only a slight fall in actomyosin ATPase activity. Ca2+-ATPase and actin-activated ATPase activities of pure myosin were similarly depressed in preparations from hearts of diabetic animals. Sodium dodecylsulfate gel electrophoresis and isoelectric focusing failed to reveal differences in the patterns of contractile proteins or light subunits between diabetics and controls, but pyrophosphate gels showed a shift in the myosin pattern. Because of depressed circulating thyroid hormone levels in diabetic animals, cardiac contractile proteins were also studied in preparations from thyroidectomized rats. Calcium activities of actomyosin and myosin ATPase were lower than values found in hearts of diabetic rats. When diabetic animals were kept euthyroid with thyroid replacement, actomyosin ATPase activity was still depressed. Thus STZ diabetes causes a significant decrease in cardiac contractile protein ATPase activity. This may be related to altered proportions of myosin isoenzymes.
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PMID:The effect of streptozotocin-induced diabetes in rats on cardiac contractile proteins. 645 19

By means of pyrophosphate electrophoresis the myosin isoenzyme pattern of two fast-twitch skeletal muscles (extensor digitorum longus, gastrocnemius) and one slow-twitch muscle (soleus) was investigated in control rats and was compared with that of rats 4 weeks after induction of diabetes mellitus by streptozotocin injection. In the fast-twitch muscles the isomyosin pattern consisting of FM1 (fast isomyosin 1), FM2 and FM3 was strongly affected by diabetes, resulting in an extensive loss of FM1 and a substantial decrease of FM2. These changes were also apparent when the light chains of the fast isomyosins were analysed by two-dimensional electrophoresis: LC3f (myosin light chain 3f) largely disappeared and LC2f was significantly diminished. In contrast, the isomyosin pattern in soleus muscle, consisting of SM1 (slow isomyosin 1) and SM2, was not affected by the diabetic state, and two-dimensional electrophoresis revealed a normal light-chain pattern of LC1sa, LC1sb and LC2s. These results indicate that the isomyosins of slow-twitch oxidative myofibres are more resistant to the hormonal and metabolic disorders during diabetes mellitus than are the isomyosins of fast-twitch fibres.
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PMID:Loss of fast-twitch isomyosins in skeletal muscles of the diabetic rat. 647 92

We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force relations were measured at a long (2.4-microns) and a short (1.9-microns) sarcomere length. In disease, compared with the control condition, the apparent Ca2+ sensitivity was greatly diminished at a sarcomere length of 1.9 microns but not affected at all at the long length (2.4 microns). We also examined the alterations in contractile regulatory proteins TnT and TnI by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots. The TnI band was largely unperturbed, but major changes were discerned in TnT. The normal rat heart indicated two major bands (TnT1 and TnT2) and a faint third band (TnT3); in the diabetic rat heart, there was a significant shift in intensity from TnT1 to TnT3. Since myosin isozyme shifts also accompany diabetes in the rat, we used a prototypical hypothyroid rat as well to evaluate the myosin influence in the length-induced effects on Ca2+ sensitivity. Myosin shifts during hypothyroidism were unaccompanied by significant changes in TnT, and there were also no length-dependent modifications in Ca2+ sensitivity. The findings raise the possibility that diabetic Ca(2+)-sensitivity changes in the myocardium are coupled with TnT alterations. A plausible explanation is offered whereby these TnT alterations modify the length dependence of Ca2+ sensitivity.
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PMID:Diminished Ca2+ sensitivity of skinned cardiac muscle contractility coincident with troponin T-band shifts in the diabetic rat. 753 60

Necrobiosis lipoidica (NL), a skin disease, is associated with insulin-dependent diabetes mellitus (IDDM). Natural autoantibody (NAb) activity in sera from 16 patients suffering from NL, with or without IDDM, was compared to that in sera from 41 patients with IDDM and 43 healthy controls. Isotype-specific enzyme-linked immunosorbent assays (ELISAs) were used to detect NAbs against actin, myosin, keratin, desmin, troponin, tropomyosin, thyroglobulin, insulin, single-stranded DNA and the hapten trinitrophenyl. NAb activity was significantly higher in sera from patients with NL (either with or without IDDM), compared with that detected in sera from patients with IDDM which was similar to that of healthy individuals. High proportion of NL sera exhibited increased IgG anti-tropomyosin (69%), anti-troponin, anti-desmin and anti-keratin (50% each), anti-insulin (44%) and anti-trinitrophenyl (31%) activities, as well as increased IgA and IgM anti-keratin activities (26% and 31%, respectively). The great majority (88%) of positive sera were polyreactive and contained NAbs, polyspecific and monospecific (as demonstrated by immunoadsorption studies), belonging to more than one isotype; there was no predominant serological reactivity pattern. In conclusion, increased NAb activity to cytoskeleton proteins is associated with the dermatological disease NL and not to the overlapping autoimmune disease (IDDM). The origin and significance of these NAbs is discussed.
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PMID:Increased natural autoantibody activity to cytoskeleton proteins in sera from patients with necrobiosis lipoidica, with or without insulin-dependent diabetes mellitus. 757 89

The severity and frequency of atherosclerosis, diabetes, and ischemic heart disease, which affect cardiac function, increase with aging. Although there are many reports about hemodynamic and histopathological studies about aging hearts, there are very few studies on changes in structural proteins in aging hearts. We investigated the contractile proteins of the left ventricles in rats aged 6, 12 and 125 weeks using two-dimensional electrophoresis. There were no difference in structural proteins in heart between 6-week and 12-week-old rats. The contents of myosin heavy chain, myosin light chain 2, actin, troponin-I in 125-week-old rats decreased compared with those of 12-week-old rats. Myosin heavy chain, which is one component of myosin, interacts with actin and changes chemical energy to mechanical energy. Therefore its decrease leads to a decline in myocardial contractility. These results seem to indicate one of the most important changes in the aging rat heart, as well as impairment in relaxation by the increase of interstitial fibrosis and decline of Ca uptake by sarcoplasmic reticulum.
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PMID:[Analysis by two-dimensional electrophoresis of the cause of myocardial dysfunction in aging rat hearts]. 836 Oct 80

Diabetic cardiomyopathy, a condition characterized by the accumulation of carbohydrate-containing material surrounding the myocardial small blood vessels, has been studied in alloxan-diabetic normotensive and hypertensive rats. Immunochemical techniques were used to monitor several extracellular matrix constituents present in extracts of cardiac tissue, namely types I, IV and VI collagen, laminin and fibronectin, as well as myosin. These studies have indicated that after induction of diabetes, type VI collagen but none of the other matrix components studied, was significantly increased (from 2.29 +/- 0.04 mg/g in normal to 2.85 +/- 0.18 mg/g in diabetic ventricles, p < 0.01). Hypertension, whether induced by the clipping of one renal artery or genetically determined (spontaneously hypertensive rats), resulted in a similar elevation in type VI collagen (2.71 +/- 0.12 mg/g, p < 0.005 compared to normal rats). In the presence of diabetes plus hypertension the effect was not additive, the type VI collagen level being 2.93 +/- 0.15 (p < 0.001 compared to normal rats). Basement membrane collagen (type IV) in the myocardium appeared to be unaffected by diabetes or hypertension and the myosin contents of the hearts of the four experimental groups were similar. Quantitative determinations indicate that compared to type IV collagen, laminin or fibronectin, type VI collagen represents the major periodic acid-Schiff-reactive extracellular constituent of the rat ventricle. Its preferential increase in the heart in diabetes may provide insight into the molecular mechanisms of the diabetic microvascular disease.
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PMID:Increased rat myocardial type VI collagen in diabetes mellitus and hypertension. 845 34

Our group has documented that myocardial performance is impaired in the hearts of chronically diabetic rats and rabbits. Abnormalities in the contractile proteins and regulatory proteins may be responsible for the mechanical defects in the streptozotocin (STZ)-diabetic hearts. Previously, the major focus of our research on contractile proteins in abnormal states has concentrated on myosin ATPase and its isoenzymes. Our present study is based on the overall hypothesis that regulatory proteins, in addition to contractile protein, myosin contribute to altered cardiac contractile performance in the rat model of diabetic cardiomyopathy. The purpose of our research was to define the role of cardiac regulatory proteins (troponin-tropomyosin) in the regulation of actomyosin system in diabetic cardiomyopathy. For baseline data, myofibrillar ATPase studies were conducted in the myofibrils from control and diabetic rats. To focus on the regulatory proteins (troponin and tropomyosin), individual proteins of the cardiac system were reconstituted under controlled conditions. By this approach, myosin plus actin and troponin-tropomyosin from the normal and diabetic animals could be studied enzymatically. The proteins were isolated from the cardiac muscle of control and STZ-diabetic (4 weeks) rats. Sodium dodecyl sulfate gel electrophoretic patterns demonstrate differences in the cardiac TnT and TnI regions of diabetic animals suggesting the different amounts of TnT and/or TnI or possibly different cardiac isozymes in the regulatory protein complex. Myofibrils probed with a monoclonal antibody TnI-1 (specific for adult cardiac TnI) show a downregulation of cardiac TnI in diabetics when compared to its controls. Enzymatic data confirm a diminished calcium sensitivity in the regulation of the cardiac actomyosin system when regulatory protein(s) complex was recombined from diabetic hearts. Actomyosin ATPase activity in the hearts of diabetic animals was partially reversed when myosin from diabetic rats was regulated with the regulatory protein complex isolated from control hearts. To our knowledge, this is the first study which demonstrates that the regulatory proteins from normal hearts can upregulate cardiac myosin isolated from a pathologic rat model of diabetes. This diminished calcium sensitivity along with shifts in cardiac myosin heavy chain (V1-->V3) may be partially responsible for the impaired cardiac function in the hearts of chronic diabetic rats.
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PMID:Troponin subunits contribute to altered myosin ATPase activity in diabetic cardiomyopathy. 856 62


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