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

Alterations in heme biosynthetic and degradative capabilities and in the activities of several heme-containing enzymes were examined in hepatic tissues of streptozotocin (STZ)-diabetic female Sprague-Dawley rats. Activities were measured 10, 30 and 90 days following the administration of STZ (65 mg/kg, i.v.). The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, and uroporphyrinogen synthase, were decreased markedly in STZ-diabetic rats as compared to sham-operated animals. Furthermore, the catabolism of heme which occurs via microsomal heme oxygenase (MHO) remained unaltered in these animals. Microsomal content of heme and cytochrome P-450, and the activities of tryptophan pyrrolase and the drug-metabolizing enzymes benzo[a]pyrene (BP) hydroxylase and aniline hydroxylase, were increased in the livers of diabetic rats. By contrast, the activity of the heme-containing enzyme catalase was decreased in these animals. Cobalt chloride produced a marked increase in MHO with a concomitant decrease in microsomal content of cytochrome P-450 and its associated BP hydroxylase activity in normal as well as chronically diabetic rats. It was of interest, however, that the increase in ALA synthase that is normally produced by this metal was not seen in chronic diabetic animals. Thus, chronic diabetes produced subtle and important disruptions in cellular metabolism, which may have been the result of long-term alterations in key enzymes involved in heme synthesis.
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PMID:Heme and hemoproteins in streptozotocin-diabetic female rats. 668 50

Monolayer cell cultures from pancreatic islets of aging 129/J strain diabetes (db3J/db3J) and lean littermate control mice were tested for differences in glucagon and insulin secretion in either serum-free Eagle's minimal essential medium (MEM) or Dulbecco's modified minimal essential medium (DMEM). There was a highly significant (p less than 0.0001) main effect of genotype and type of culture medium on glucagon secretion with time. Thus, although numbers of A-cells were not demonstrably increased in db3J/db3J cultures in DMEM, mean medium glucagon levels increased 2.7-, 18-, and 32-fold above littermate normal culture levels at days 4, 6, and 8 respectively. In MEM, the two populations could not be discriminated on the basis of glucagon secretion. By contrast, insulin secretion over culture days showed a highly significant (p less than 0.0001) dependence on genotype, but not type of medium, with the B-cell enriched db3J/db3J preparations secreting between 20 and 30 times as much insulin as controls in both medida. Analysis revealed that the heightened secretory responsiveness of mutatn A-cells in DMEM as compared to MEM was primarily elicited by the elevated DMEM amino acid concentration and specifically lysine (0.8 mmol/l in DMEM versus 0.4 mmol/l in MEM). In pulse-chase experiments using 14 day db3J/db3J cultures, incorporation of 3H-tryptophan into protein that eluted from Biogel P-10 columns in the native glucagon peak indicates that DMEM stimulated glucagon biosynthesis as well as secretion. This study reveals an augmented sensitivity of db3J/db3J A-cells to stimulation by basic amino acids in long-term culture.
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PMID:A new mutation (db3J) at the diabetes locus in strain 129/J mice. II. Studies of pancreatic alpha cell function in culture. 699 70

Rat pancreatic islets were incubated in vitro with L-[4,5-3H]leucine or with L-[2,3-3H]tryptophan in Krebs-Ringer bicarbonate buffer, containing 0, 5, or 20 mM glucose. Incorporation of labeled amino acids in islet cells was evaluated quantitatively by a validated radioautographic procedure. Incorporation of labeled leucine into [3H]proinsulin and [3H]insulin was measured by immunoprecipitation and into other islet proteins by trichloroacetic acid precipitation. Incorporation of labeled amino acids in pancreatic beta cells was patchy and not uniform. Up to 20 to 35% of beta cells, mainly in central regions of the islets, showed poor or no incorporation of label. Peripheral nonbeta, endocrine islet cells and mesenchymal islet cells were all uniformly labeled. Incorporation of either amino acid into nonbeta endocrine and mesenchymal cells was not much affected by the absence of glucose in the incubation buffer. In contrast, incorporation of the amino acids into beta cells was strikingly affected. Incorporation of [3H]leucine into proinsulin and insulin at 0 mM glucose measured by specific immunoprecipitation and by silver grain densities over beta cells was 15 to 20 times less than at 20 mM glucose. Incorporation of [3H]tryptophan, an amino acid absent in proinsulin, into nonhormonal, sedentary beta cell proteins studied by radioautography, similarly, was strikingly affected in the absence of glucose. Thus, radioautography revealed a great sensitivity of both hormonal and nonhormonal protein biosynthesis in the beta cell to the concentration of glucose in the medium.
Diabetes 1980 Oct
PMID:Biosynthesis of proinsulin and other islet cell proteins in pancreatic beta cells of the rat: a radioautographic evaluation of glucose effects in vitro. 700 60

Rats were infused for brief periods with buffer, glucose, or insulin. L-[4,5-3H] leucine (2.5 mCi) or L-[2,3-3H]-tryptophan (0.5 mCi) was quickly injected intravenously 30 min after the onset of the infusion, when marked hyperglycemia or hypoglycemia had been established. Rats remained connected to the infusion system and were killed 30 min after the injection of the labeled amino acid. Pancreatic islets were isolated by enzymatic digestion of the pancreas. They were processed for radioautography or for the measurement of [3H] proinsulin and [3H] insulin by immunoprecipitation and of other islet [3H] proteins by TCA precipitation. Various tissues of the rats were also removed to measure TCA-precipitable-labeled proteins. Incorporation of [3H]-leucine into proinsulin and insulin was 9 to 20 times greater in the hyperglycemic than in the hypoglycemic rats. Incorporation of [3H]-tryptophan into sedentary beta-cell proteins, measured by thea density of silver grain in radioautographs, showed a sixfold difference. The great sensitivity of hormonal and nonhormonal protein biosynthesis of the pancreatic beta cell to plasma glucose was unique among tissues and among other pancreatic islet cells we studied.
Diabetes 1980 Oct
PMID:In vivo incorporation of [3H[ leucine and [3H] tryptophan into proinsulin-insulin and other islet cell proteins in normoglycemic, hyperglycemic, and hypoglycemic rats. 700 61

Because the supplementation of pyridoxine (vitamin B6) improves the glucose tolerance in gestational diabetes and adult onset diabetes, pyridoxine deficiency has been considered to be one of the factors that cause diabetes mellitus. We produced pyridoxine deficient rats by giving pyridoxine-free food with deoxypyridoxine which competitively the activity of pyridoxal phosphate. In these pyridoxine deficient rats plasma insulin during the glucose tolerance test was significantly low as compared with controls. In vitro experiments of pancreas perfusion showed that secretion of insulin and glucagon was impaired in the pyridoxine deficiency. Since the restriction of diet-calorie caused a decrease in arginine-induced secretion of insulin and glucagon from the isolated pancreas, the impairment of the endocrine pancreas may depend on malnutrition. Pyridoxine deficiency is surely one of the factors that impair the endocrine pancreas by multifactorial derangement of metabolism besides the tryptophan-nicotinic acid pathway.
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PMID:The endocrine pancreas in pyridoxine deficient rats. 703 87

The regulation of tryptophan-niacin metabolism by pituitary and adrenocortical hormones was investigated. Hypophysectomized rats fed on a niacin-free purified diet were injected with bovine somatotropin, predonine acetate or both. The urinary excretion of N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2-Py) after oral administration of tryptophan was then compared before and after the hormone treatment. The amount of urinary MNA was found to be increased after the injection of somatotropin, but decreased after the predonine injection. On the other hand, no change in urinary MNA was observed in the rats administered with both hormones. The amount of 2-Py appeared to be reduced by the predonine treatment, but was not affected by somatotropin injection. The activity of liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (picolinic carboxylase) was shown to be directly proportional to the ratio (oral tryptophan)/(urinary MNA). Moreover, the enzyme activity appeared to be inversely proportional to the concentration of niacin in liver. In addition, the amount of urinary MNA was suggested to be affected by the change of body weight gain. The administration of both pituitary hormone and insulin failed to normalize the reduced urinary MNA excretion in diabetic rats, suggesting that any change in pituitary hormone was not responsible for the abnormal tryptophan-niacin metabolism in diabetes.
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PMID:Regulation of tryptophan-niacin metabolism by hormones. 724 Dec 42

The prevalence of cataracts is significantly lower in patients with rheumatoid arthritis receiving aspirin (mean of 2,700 mgs daily for an average of 10.4 years) as compared to the matched population not receiving aspirin. Similarly, fewer cataracts were found among a population with diabetes and rheumatoid arthritis receiving aspirin (mean of 2,340 mgs daily for an average of 8.8 years) as compared to the matched population on no aspirin. The effects of aspirin on cataract formation may result from 1) lowering of plasma tryptophan levels and increased excretion of tryptophan metabolites, 2) inhibition of aldose reductase and sorbitol formation in the diabetic lens, 3) inhibition of tryptophan or kynurenine binding to lens protein.
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PMID:Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined with diabetes. 726 27

The changes of brain tryptophan and 5-HT levels have been explored in the diabetic rat during the first hour after an intraperitoneal load of tryptophan. The obtained data confirm that diabetes decreases the basal levels of tryptophan but not those of 5-HT. Also, it has been shown that diabetes remarkably depresses the rate of the aminoacid accumulation and almost completely inhibits the rise of 5-HT after the tryptophan load.
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PMID:[Effects of a tryptophan load on brain levels of serotonin in normal and diabetic rats]. 727 46

A method is described for determining the natural progression of senile cataracts in humans and whether certain factors accelerate or decelerate this progression. The method consists in plotting the age of the patient against the degree of opacity of the cataract to find the regression relation. A comparison of cataracts from diabetic and nondiabetic patients revealed that diabetes accelerated senile cataract formation, so that there was a difference of 9.6 years in the age of the two groups with more dense cataracts. Plasma tryptophan levels, which are increased in cataract patients, are lowered by acetylsalicylic acid (ASA). In this study ASA decelerated cataract formation in diabetic and nondiabetic patients. Among the nondiabetic patients cataract formation in a group with osteoarthritis was delayed by an average of 10 years. Deceleration of cataract formation resulting from ASA administration may reduce the need for surgical removal of cataracts.
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PMID:Senile cataracts: evidence for acceleration by diabetes and deceleration by salicylate. 729 56

The present study was conducted to examine whether experimental diabetes (streptozotocin-induced) promotes changes in serotonin (5HT) measures of peripheral tissue. Platelet-free plasma 5HT, tryptophan and 5-hydroxyindolacetic acid (5HIAA), whole blood 5HT and renal, liver, intestinal and lung 5HT and 5HIAA levels were measured in rats of four experimental groups: control, diabetic, diabetic+insulin and non-diabetic+insulin. Several serotonin measures were unaltered in all four experimental groups, i.e. plasma, liver and lung 5HT and 5HIAA levels. Whole blood 5HT levels descended about 50% in diabetic rats, then recovered their proper levels after 1 week of insulin therapy. Diabetic animals had a significantly greater intestinal 5HT concentration (+50% versus control), while intestinal 5HIAA levels did not achieve statistical significance despite a -26% decrement in their value. Both renal 5HT and 5HIAA levels were decreased in diabetic animals and recovered with insulin therapy. Peripheral tissue 5HT measures were not varied by insulin administration to non-diabetic animals. The results are consistent with a 5HT release, which is diminished in enterochromaffin cells and enhanced in platelet concomitantly to a minor platelet 5HT uptake, for explaining alterations of plasma/blood 5HT measures in experimental diabetes, and with a diminished synthesis of 5HT for explaining renal changes.
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PMID:Effect of streptozotocin-induced diabetes mellitus on serotonin measures of peripheral tissues in rats. 753 Mar 14


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