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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes produced by injection of alloxan or streptozotocin results in cardiac dysfunction in rats that is associated with lower cardiac contractile protein ATPase activity. The purpose of this investigation was to examine cardiac myosin biochemistry in the Bio-Breeding Worcester (BB/W) rat, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. Hearts from diabetic BB/W rats were studied at 1, 4, and 7 mo after the onset of diabetes and were compared with age-matched BB/W rats that were bred for resistance to diabetes. Calcium-stimulated myosin ATPase activity was significantly decreased after 4 and 7 mo of diabetes, and actin-activated myosin ATPase was significantly depressed at all time points. Differences between hearts from control and diabetic animals increased with the duration of diabetes. Closely associated with reductions in myosin ATPase activity in the diabetes was a shift in the isomyosin content from the normally predominant V1 to the V3 isoenzyme. Thus diabetes that results from genetic causes leads to depressed myosin enzymatic activity in the rat. Furthermore, since previous studies have shown that BB/W diabetic rats do not develop hypothyroidism, the present results support the view that altered thyroid function does not mediate the abnormalities in cardiac contractile proteins in diabetes.
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PMID:Abnormal cardiac biochemistry in spontaneously diabetic Bio-Breeding/Worcester rat. 293 20

The present study provides histochemical evidence supporting the operation of the 'glucose-fatty acid cycle' in skeletal muscles taken 5 days after the administration of a single injection of streptozotocin. It also indicates that the cycle is more important in fast-oxidative-glycolytic (FOG) and slow-oxidative (SO) fibres than in fast-glycolytic (FG) fibres. Data from muscles taken 14 and 28 days after treatment suggest that lipid catabolism becomes progressively less important with time, and that muscles from longer-term diabetic rats rely on the aerobic and anaerobic breakdown of glucose by FOG and FG fibres to meet their cellular energy requirements. Although SO fibres appeared initially to be the least affected by streptozotocin-induced diabetes, the decline in their metabolic capabilities ultimately seemed to be greater than that in FOG fibres. Transformations in the biochemical characteristics of FOG and SO fibres occurred 14-28 days after streptozotocin treatment, in the absence of changes in actomyosin-ATPase activity. This supports the view that the division of skeletal muscle fibres into three or four distinct types on the basis of myosin- or actomyosin-ATPase activity is an oversimplification of the true situation.
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PMID:Histochemical evidence of changes in fuel metabolism induced in red, white and intermediate muscle fibres of streptozotocin-treated rats. 294 22

In rats, chronic diabetes is associated with depressed cardiac myosin ATPase activity and a shift from the predominant V1 isoenzyme to V3, correlating with depressed contractility. Rabbit myocardium consists mostly of the V3 isoenzyme, and therefore a switch to even more V3 isoenzyme in diabetes might not be possible and therefore not explain the mechanical abnormalities observed. To explore this, rabbits were made diabetic with 140-150 mg/kg of alloxan, and their hearts were studied 3 days, 1 mo, 3 mo, and 6 mo later. Ca2+-myosin-ATPase activity was decreased in the diabetic rabbit at 1, 3, and 6 mo, correlating with increased percent V3. Actin-activated Mg2+-ATPase activity was not significantly decreased in diabetics, but myofibrillar ATPase activity was decreased in 6-mo diabetic animals. When 3- to 4-mo diabetic animals were administered insulin for 3-4 additional months, myosin-ATPase activity and isoenzyme distribution normalized. These results correlate well with mechanical changes in papillary muscle from these same hearts. They suggest that in rabbit, as in rat, changes in cardiac contractile function are at least partially mediated by changes in myosin isoenzyme composition and are reversible with insulin.
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PMID:Effects of diabetes on cardiac contractile proteins in rabbits and reversal with insulin. 294 66

The ATPase activity of myofibrils and myosin from hindlimb muscle was investigated in animals 4 wk after the induction of diabetes by an intravenous injection of streptozotocin (65 mg/kg). Ca2+-stimulated ATPase in myofibrils was increased in diabetic muscle at various times of incubation (1-7 min) as well as at different concentrations of free Ca2+ (10(-7)-10(-5) M Ca2+). Such an increase in Ca2+-stimulated ATPase was evident as early as 1 wk after streptozotocin injection, but Mg2+-ATPase activity remained unaltered. Treatment of diabetic animals with insulin Ca2+-ATPase and actin-activated ATPase activities of pure myosin were similarly increased in diabetic muscle. Myosin ATPase was also activated by K+- or NH4+-EDTA; these responses were more in diabetic muscle. However, sodium dodecyl sulfate gel electrophoresis failed to reveal differences in the patterns of contractile proteins, and pyrophosphate gels did not show significant changes in myosin isozyme patterns between diabetics and controls. The results of this study demonstrate an activation of contractile protein ATPase of skeletal muscle in diabetes and seem to indicate that such an alteration may be responsible for enhanced contractile function of skeletal muscle in this disease.
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PMID:Altered contractile proteins in skeletal muscle of diabetic rats. 295 57

One of the central, unresolved problems in our understanding of insulin secretion is the way in which stimulus recognition and its associated metabolic events are translated into the mechanical processes of insulin-storage granule movement and extrusion from the cells by exocytosis. In the present article we have examined the structural organization of the B-cell cytoskeleton in detail and have reviewed how drugs that affect the cytoskeleton alter insulin secretion. Available information about the interactions of tubulin, actin, myosin, and actomyosin with insulin-secretory granules is summarized, and a tentative model is proposed to explain how stimulus-effector system coupling might be achieved.
Diabetes Metab Rev 1986
PMID:The cytoskeleton and insulin secretion. 301 43

In the rat heart diabetes mellitus leads to a change in myosin heavy chain (MHC) mRNAs and corresponding alterations in myosin isoenzymes as well as a decrease in total cardiac protein synthesis. However, it is still unknown whether cardiac proteins other than MHC are altered by diabetes and if so whether these abnormalities are mediated by insulin deficiency. To answer these questions we analyzed proteins synthesized by isolated cardiac myocytes in the presence or absence of insulin. Enzymatically dispersed adult cardiac myocytes from control and streptozotocin-induced diabetic rats were incubated in medium containing [35S]-methionine for 4 h; diabetic cells were incubated with or without the addition of 5 x 10(-7)M insulin. The labelled peptides were then separated by two-dimensional polyacrylamide gel electrophoresis and analyzed by fluorometry. The abundance of six individual polypeptides was consistently affected by diabetes: one protein was significantly decreased while four others were increased in diabetic myocytes. The remaining protein showed a shift in isoelectric point without a change in molecular weight possibly representing isoforms of a single polypeptide. The addition of insulin reverted the predominance of three proteins back to normal while it did not affect the other three at all. In conclusion diabetes induces changes in the abundance of a few proteins synthesized in vitro by cardiac myocytes and only half of them show an acute response to insulin.
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PMID:Diabetes-induced changes of proteins synthesized by adult cardiac myocytes are partially reversed by insulin. 306 85

Previous studies have shown that in rats diabetes mellitus leads to a decrease in cardiac ventricle myosin V1 and an increase in myosin V3 levels. Insulin administration reverts myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on myosin isoenzyme distribution are a direct effect of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To gain further insight into this question diabetic rats received methyl palmoxirate, a potent inhibitor of long-chain fatty acid oxidation. Administration of 25 mg methyl palmoxirate X kg body wt-1 X day-1 to diabetic rats for 4 wk leads to a partial reversal of the effects of diabetes. Myosin V1 predominance is re-established and Ca2+-activated myosin ATPase activity increases by 60% (Ca2+-myosin ATPase normal rats 1.067 +/- 0.13 mumol Pi X mg protein-1 X min-1, diabetic rats 0.609 +/- 0.05 mumol Pi X mg protein-1 X min-1, diabetic + methyl palmoxirate rats 0.912 +/- 0.06 mumol Pi X mg protein-1 X min-1). The methyl palmoxirate-induced increase in myosin V1 levels and Ca2+-activated myosin ATPase activity occurred in the absence of changes in insulin and thyroid hormone levels. Methyl palmoxirate may have acted through its known inhibitory effect on cardiac beta-oxidation and/or the resultant stimulatory effect on glycolytic flux. Our findings may indicate that changes in cardiac substrate consumption can influence myosin isoenzyme predominance.
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PMID:Methyl palmoxirate increases Ca2+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. 315 15

Isolated pancreatic acini from streptozocin-induced diabetic rats were used to study the role of insulin on the synthesis of specific cellular proteins. When acini were incubated with 0-100 nM insulin for 2 h and then pulsed with [35S]methionine, a dose-dependent increase in [35S]methionine incorporation into total cellular proteins was observed. When acinar cell lysates were subjected to gel electrophoresis, 12 major newly synthesized protein bands were resolved. Insulin (100 nM) increased the incorporation of [35S]methionine into all bands but with significantly different rates, varying from 84 to 216% of control. Next, specific antibodies to amylase, trypsin, ribonuclease, myosin, and lactate dehydrogenase (LDH) were used to evaluate the biosynthesis of known proteins. Insulin stimulated labeled amino acid incorporation into amylase by 148% over control. Insulin stimulated the synthesis of trypsinogen to a similar degree, but ribonuclease synthesis showed a significantly smaller increase of 53% over control. Insulin stimulated myosin and LDH synthesis by 169 and 184%, respectively. A differential pattern of protein synthesis was also observed when acini were treated with two other stimulators of protein synthesis, cholecystokinin and hemin. Both of these stimulators had a reduced effect on ribonuclease synthesis compared with amylase and trypsinogen synthesis but failed to increase myosin synthesis. When the RNAs extracted from control acini and acini treated with 100 nM insulin were translated in vitro, the proteins synthesized were quantitatively similar. This study therefore indicates that insulin has translational effects on acinar protein synthesis, and these effects are nonparallel for various specific acinar cell proteins.
Diabetes 1987 Sep
PMID:Insulin and other stimulants have nonparallel translational effects on protein synthesis. 330 74

Previous studies have shown that diabetes mellitus leads in rats to a 45% decrease in cardiac Ca++ activated myosin ATPase, a change in myosin isoenzyme distribution and a lowering of plasma T4 and T3 levels. Hypothyroidism causes similar changes in myosin ATPase and myosin isoenzyme distribution. We determined if thyroid hormone administration in physiological replacement dose (0.3 microgram T3/100 g BW) or pharmacological doses (3 micrograms T3/100 g BW and 10 micrograms T4/100 g BW) can normalize myosin ATPase and isoenzyme distribution in diabetic rats. Control animals have a Ca++ myosin ATPase activity of 1.23 +/- 0.14 mumol Pi/mg protein/min and myosin V1 represented 70% and myosin V3 15% of total myosin. Four weeks after streptozotocin administration myosin ATPase was 0.61 +/- 0.14, and myosin V3 represented 67% of total myosin. Administration of 0.3 microgram T3/100 g BW/day for four weeks to diabetic animals resulted in no significant increase in myosin ATPase (0.69 +/- 0.07 mumol Pi/mg protein/min) or in myosin isoenzyme distribution. In contrast, administration of 3 micrograms T3/100 g BW/day or 10 micrograms T4/100 g BW/day for 4 wk led to a normalization of myosin ATPase activity (for T3 1.03 +/- 0.18, for T4 1.06 +/- 0.15). In addition the myosin isoenzyme distribution pattern normalized. These findings may point to a diminished thyroid hormone responsiveness in diabetic rats or could result from diabetes related disturbances of cellular metabolism, which are normalized by pharmacologic doses of thyroid hormone.
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PMID:Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. 621 Aug 24

The effects of insulin, T4, and T3 treatment on cardiac function, myosin ATPase activity, and myosin isozyme distribution were studied in alloxan diabetic rats. Diabetes resulted in depressed peak ventricular pressure development, heart rate, and left ventricular +dP/dt. Myocardial Ca2+-activated myosin ATPase activity was reduced in association with lower serum levels of T3 and T4. The V1 isozyme of myosin decreased, and both V2 and V3 isozymes increased. Insulin treatment totally reversed the changes in function, serum thyroid hormones, and myosin ATPase activity. Treatment of diabetic animals with T4 (5 or 10 micrograms/day) prevented the decrease in myosin ATPase but did not prevent the changes in cardiac function, myosin isozymes, or serum T3 levels. Pharmacological doses of T3 (3 micrograms/day) that were adequate to maintain higher than normal serum T3 corrected the decrease in Ca2+-activated myosin ATPase and heart rate but only partially corrected the changes in pressure development and myosin isozyme distribution. Only when serum T3 was increased to four times normal was cardiac function corrected.
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PMID:Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4. 622 Jun 14


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