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

The muscle protein lost in uncontrolled diabetes may be due to decreased synthesis, increased catabolism, or to any combination of alteration in these rates that results in net loss. Differing methods of examining these rates in vivo and in vitro have given conflicting results. We assessed the rate of catabolism of proteins containing 3-methylhistidine (3-MH) by measurement of its urinary excretion in spontaneously diabetic "BB" Wistar rats. Prior to overt diabetes, rates of excretion were appropriate to the age of the rats (1.46 +/- 0.15 mumole/day), with 34%-47% as the nonacetylated form. Accompanying diabetes there was an increase in urine urea nitrogen of two to threefold over 4-14 days, and an increase in ammonium nitrogen of sixfold. 3-MH excretion doubled by 4 days, and 81%-96% was excreted as the nonacetylated form. Subcutaneous insulin in doses sufficient to improve glycosuria and hyperglycemia was associated with normalized total 3-MH excretion (N-acetyl 3-MH plus 3-MH) but a greater proportion than normal appeared in the nonacetylated form. These results suggest that muscle protein catabolism increased with insulin deficiency and that this defect can be corrected by therapy. Both untreated and treated diabetic rats appear to have a limited capacity for acetylation of 3-MH prior to its excretion.
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PMID:Muscle protein catabolism in diabetes: 3-methylhistidine excretion in the spontaneously diabetic "BB" rat. 700 19

The effects of a 20% dorsal scald injury and of different severities of streptozotocin diabetes on hindquarter muscle protein have been studied in the mouse. Ten days after scald injury muscle protein contents were generally unaffected, whereas moderate diabetes (200 mg streptozotocin/kg body weight; plasma glucose concentrations 17--46 mmol/1; normal 11 mmol/l) led to net loss of muscle protein. Production of scald injury in the moderately diabetic mouse caused significant additional loss of muscle protein, especially from the extensor digitorum longus Milder diabetes (maximum plasma glucose concentration 15 mmol/l) did not lead to loss of muscle protein. However, scald injury in the mildly diabetic mouse caused significant loss of protein from all muscles studied. The effects of diabetes and of injury on loss of muscle protein were at least additive and in some muscles probably synergistic.
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PMID:Effects of diabetes and of injury on muscle protein in the mouse, and their interaction. 700 92

Proteolytic enzyme activities were measured in skeletal muscle of Sprague-Dawley rats with streptozotocin-induced diabetes [tail vein injection of streptozotocin (100 mg/kg), under ether anesthesia]. Assay of rat muscle homogenates from diabetic rats revealed a significant increase in alkaline serine protease activity as compared to untreated control rats and diabetic rats given insulin. There were no significant changes in lysosomal cathepsin activities in diabetic muscle as compared to controls. Gel studies of myofibrils isolated from the three groups of rats, subjected to autolysis, revealed that the serine protease had copurified with the myofibrils. Treatment of rats with compound 48/80, which degranulates mast cells, abolished the alkaline protease activity. There was no serine protease activity associated with the myofibrils isolated from compound 48/80-treated rats. Results from this study indicate that serine proteases are not involved in muscle protein breakdown in diabetes and are of mast cell origin.
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PMID:Muscle proteolytic enzyme activities in diabetic rats. 703 84

To test the effects of acute cold on muscle amino acid and protein 1) rats were exposed to 4 degrees C for 24 h, functionally hepatectomized (eviscerated) and accumulation in the blood used to indicate changes in amino acid release from the tissues; 2) other rats were left intact, and urinary excretion of 3-methylhistidine (proportional to muscle protein breakdown) determined during cold exposure. In the eviscerated group, cold enhanced loss of total amino acids from the tissues (as alpha-amino nitrogen), but the loss (213 +/- 14.8% of basal in 2 h) was not due to excess alanine (180 +/- 8.5%). By comparison, in fasted rats total amino acid was 182 +/- 12.3, alanine 309 +/- 17.2%. Also, the cold-induced loss resembled the effects of streptozotocin diabetes and depended on a depression by cold of serum insulin (to 35.7 +/- 2.3 muU/ml). Therefore it was prevented when insulin was restored by infusion (40 mU . 100 g-1 . h-1) or by adrenodemedullation before cold exposure. Epinephrine (10 micrograms/100 g sc) depressed insulin in the latter and permitted amino acid release to recur. In intact rats, 3-methylhistidine excretion was unaffected by cold. The results suggest that although cold fails to stimulate alanine synthesis or protein breakdown, it inhibits insulin release sympathetically, thereby diminishing the amount of amino acid incorporated into muscle protein.
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PMID:Effects of acute cold exposure on muscle amino acid and protein in rats. 704 71

In an attempt to evaluate muscle protein catabolism in patients with uncontrolled diabetes, urinary excretion of 3-methylhistidine was measured in eight diabetic subjects, during poor control and after achievement of satisfactory control. The results were compared with the excretion values of ten healthy subjects fed a similar amount of meat. In the diabetic patients in poor metabolic control, 3-methylhistidine excretion was significantly increased compared with the healthy subjects, and returned to normal when a satisfactory glycaemic control was achieved. No significant differences were observed between ketonuric and non-ketonuric uncontrolled patients. Improved glycaemic control reduced 3-methylhistidine excretion in both insulin-dependent and non-insulin-dependent diabetes. These results suggest increased protein catabolism causing muscle protein loss and negative nitrogen balance in diabetic patients with poorly controlled disease.
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PMID:Muscle protein breakdown in uncontrolled diabetes as assessed by urinary 3-methylhistidine excretion. 717 22

It is clear that the anthropometric ramifications, especially with respect to muscle mass, of the metabolic actions of GH and IGF-I treatment in intact and GH-deficient adults require further study. At present, it appears that daily GH or IGF-I treatment modestly increases nitrogen retention in most normal adults, probably by separate but permissive mechanisms, but only for a short period of time (approximately 1 month). During prolonged GH administration, resistance to the anabolic actions of GH seems to occur, and optimizing the anabolic effects of GH or IGF-I treatment will require a better understanding of the interactions among GH, GHBP, IGF-I production, IGFBPs, the GH dose regimen, and other unidentified regulatory factors. On the basis of the similar increases in muscle protein synthesis, muscle cross-sectional area, and muscle strength observed in placebo and GH-treated exercising young adults, it is doubtful that the nitrogen retention associated with daily GH treatment results in an increase in contractile protein, improved muscle function, strength and athletic performance. Even in catabolic or GH-deficient populations, GH treatment provides only modest increments in nitrogen retention, muscle size, strength, and exercise capacity. Further, the side effects of GH treatment (water retention, carpal tunnel compression, insulin resistance) would be a detriment, rather than an aid, to athletic performance. In addition, whether prolonged (> 6 months) GH treatment alone or in combination with other agents used by athletes (e.g., anabolic steroids, beta-agonists) is associated with other adverse side effects (e.g., cancer, diabetes) has not been evaluated. Therefore, health professionals should continue to discourage the use of GH by exercise enthusiasts.
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PMID:Growth hormone effects on metabolism, body composition, muscle mass, and strength. 792 47

Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane. Feeding a high P/S diet increased polyunsaturated fatty acid content of major membrane phospholipids of adipocyte plasma membrane in normal and diabetic animals, increased membrane linoleic acid content, and prevented a decrease in arachidonic acid level in diabetic animals. The high P/S diet increased insulin binding in control animals. Animals fed the high P/S diet had significantly higher rates of insulin-stimulated glucose transport and lipogenesis than did animals fed the low P/S diet. Feeding a high P/S diet significantly increased the amount of glucose transported when expressed as a function of the specific amount of insulin bound. To determine if dietary fat-induced alterations in the fatty acid composition of skeletal muscle lipid alter insulin-dependent and basal muscle metabolism, contralateral epitrochlearis and extensor digitorum longus muscles were isolated and incubated in vitro. High levels of dietary omega-3 fatty acids reduced PGE2 and PGF2 alpha synthesis in extensor digitorum longus and epitrochlearis muscle. Insulin increased glucose and amino acid transport; the increase in glucose transport by insulin was significantly greater after consumption of the high omega-3 fatty acid diet. Rats fed high levels of omega-3 fatty acids showed reduced net protein degradation in the presence and absence of insulin due to decreased rates of protein degradation and synthesis. These experiments indicate that high levels of dietary omega-3 fatty acids alter muscle membrane composition, glucose transport, and metabolism of muscle protein. To determine if dietary fatty acids alter the onset of diabetes and insulin binding to liver nuclei in spontaneously diabetic rats, weanling rats were fed chow or semipurified diets containing 20% (w/w) fat of either high or low P/S ratio. Feeding a high P/S diet increased insulin binding to liver nuclei of control and diabetic animals. Although diet did not alter the onset of diabetes, insulin binding to liver nuclei is higher in animals at the onset of diabetes than in highly diabetic animals. Eight-week-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low P/S ratio to investigate the effect of diet on specific binding of insulin to liver nuclei. Insulin binding was highest in nuclei from lean mice fed a high P/S diet. Specific binding of insulin to nuclei from obese mice was also increased by the high P/S diet, but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary lipids influence insulin action. 835 37

Although insulin's anticatabolic effect on protein metabolism in type 1 diabetes has been clearly shown to be related to the inhibition of protein breakdown, insulin's effect on muscle protein synthesis remains controversial. Cross-limb studies and measurements of synthesis rates of mixed muscle protein have yielded conflicting results. These measurements represent the mean synthesis of several muscle proteins and may miss changes in the synthesis rates of individual muscle proteins. We measured the fractional synthesis rates of myosin heavy chain (MHC), the principal muscle contractile protein, and mixed muscle protein (MMP) in six type 1 diabetic patients during insulin deprivation and insulin treatment. Comparisons were made with six healthy control subjects. Muscle biopsies were taken at 2 h and 8 h during a primed continuous infusion of L-[1-13C]leucine. MHC was purified by a preparative continuous elution gel electrophoresis, and fractional synthesis rates were calculated. We found that in type 1 diabetic subjects, the fractional synthesis rates of MHC and MMP during insulin treatment are similar to those of control subjects. Acute insulin deprivation did not affect either the synthesis rate or the ratio of MHC to MMP in type 1 diabetic subjects. In the postabsorptive state, acute insulin deprivation has no effect on MHC or MMP synthesis in type 1 diabetic patients.
Diabetes 1997 Aug
PMID:Skeletal muscle myosin heavy chain synthesis in type 1 diabetes. 923 59

Experimental streptozotocin-induced diabetes resulted in important changes in body weight which were associated with abnormalities in water and food intake. In addition, diabetic rats showed a clear muscle atrophy involving a decrease in both skeletal muscle size and protein content. This was accompanied by a marked loss of total carcass nitrogen. These changes were related to important alterations in protein turnover in skeletal muscle. Thus, the diabetic animals showed changes in the fractional protein rates of both synthesis (decreased by 37%) and degradation (increased by 140%). The increased protein degradation observed in the muscle of the diabetic animals was associated with important changes in the concentration of both circulating and muscle amino acids. Interestingly, the diabetic animals did not show important changes in either liver or kidney protein turnover rates, in spite of having a clear increase (over 50%) in kidney mass. In addition, and although the total amino acid concentration was not affected by the diabetic state, the chemically induced diabetic animals showed important elevations of branched-chain amino acids (leucine, isoleucine, and valine) in both blood and skeletal muscle. Similarly, important decreases in the blood concentrations of glutamate+glutamine, alanine, glycine, proline, serine, and threonine were also observed. These observations reinforce the idea of the association between muscle protein wasting, increased protein turnover, and alterations in branched-chain amino acids previously proposed by our group.
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PMID:The increased skeletal muscle protein turnover of the streptozotocin diabetic rat is associated with high concentrations of branched-chain amino acids. 923 2

The daily turnover of protein amounts to 280 g in an adult weighing 70 kg but the metabolic processes responsible for protein turnover are only just beginning to be understood. In cells, the major pathway of protein degradation is the ubiquitin-proteasome pathway and protein flux through this pathway is precisely regulated. In catabolic conditions such as uremia, activity of the ubiquitin-proteasome pathway increases, resulting in degradation of muscle protein. In addition to increased protein degradation, gene transcription is activated, resulting in higher levels of the mRNAs encoding ubiquitin and proteasome subunits. The signals activating this pathway include metabolic acidosis and glucocorticoids but must be more diverse since the pathway is also activated in response to starvation, sepsis, cancer, muscle denervation, thermal injury, and acute diabetes. Understanding how the pathway is controlled could lead to the prevention of muscle loss in uremia and other conditions.
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PMID:Cellular mechanisms controlling protein degradation in catabolic states. 938 15


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