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)

An ascochlorin derivative, AS-6, is a new hypoglycemic agent orally active in both obese hyperinsulinemic and insulin-deficient diabetic animal models. AS-6, when given as a 0.025-0.2% admixture in the diet, dose-dependently ameliorated polydipsia, polyuria, and glycosuria in the genetically obese diabetic mouse, C57BL/KsJ db/db, while neither insulin nor tolbutamide showed any beneficial effects. The amelioration by AS-6 was associated with a marked decrease in serum glucose and triglyceride. The effects persisted at least 10 wk, accompanied by a steady decrease in drinking water consumption. The chronic treatment prevented pancreatic islet degeneration, e.g., degranulation of the beta-cells, basophilic appearance of the exocrine border around the islets, and small round cell infiltration. The isolated islets from AS-6-treated mice released much more insulin in response to glucose than those from untreated controls. A significant correlation between serum immunoreactive insulin and glucose/triglyceride from both treated and untreated mice suggests that AS-6 restores sensitivity and responsiveness to insulin to the mice. In fact, the combined treatment with insulin synergistically decreased serum glucose by 50% below AS-6 treatment alone. Furthermore, the epididymal fat pad slices from AS-6-treated db/db mice increased CO2 generation and lipogenesis over the untreated controls, and the glucose metabolic rate (CO2 generation plus lipogenesis from U-[14C]-glucose) in the slices and the serum glucose level inversely correlated at r = 0.8799.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Mar
PMID:An ascochlorin derivative, AS-6, reduces insulin resistance in the genetically obese diabetic mouse, db/db. 388 94

The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxygenase (EC 1.13.11.11) 7-8-fold, and the flux through the kynurenine pathway 3-4-fold, in cells from both control and adrenalectomized rats. Increases in flux through kynureninase (EC 3.7.1.3) and to acetyl-CoA can be explained in terms of increased substrate supply from tryptophan 2,3-dioxygenase. The metabolism of tryptophan was increased 3-fold in liver cells isolated from acutely (3 days) diabetic rats, with a 7-8-fold increase in the maximal activity of tryptophan 2,3-dioxygenase. The oxidation of tryptophan to CO2 and metabolites of the glutarate pathway increased 4-5-fold, consistent with an increase in picolinate carboxylase (EC 4.1.1.45) activity. Liver cells isolated from chronic (10 days) diabetic rats metabolized tryptophan at rates comparable with those of cells from acutely diabetic rats, but with a 50% decrease in the activity of tryptophan 2,3-dioxygenase. The proportion of flux from tryptophan 2,3-dioxygenase to acetyl-CoA, however, was increased by 50%; this was indicative of further increases in the activity of picolinate carboxylase. Administration of insulin partially reversed the effects of chronic diabetes on the activity of tryptophan 2,3-dioxygenase and flux through the kynurenine pathway, but had no effect on the increased activity of picolinate carboxylase. The role of tryptophan 2,3-dioxygenase in regulating the blood tryptophan concentration is discussed with reference to its sensitivity to the above conditions.
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PMID:The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes. 389 9

Whereas glucose is a major substrate for pulmonary lipid synthesis, fructose has also been suggested as a potential substrate. In vivo pulmonary fatty acid synthesis is depressed in hormonally deprived conditions, such as diabetes, and this can be modified by fructose feeding, but not by glucose feeding. In this study the glucose and fructose utilizations were compared in normal, diabetic and fasting states using isolated perfused rat lungs. When (U-14C)- or (5-3H)-glucose was used as substrate, glucose utilization by lung was reduced by 50% in both the fasting and diabetic animals compared to the normal controls. Using (U-14C)-glucose as substrate, the incorporation of (14C)-label in various metabolites of glucose was significantly depressed. For example, this reduction was 50% in lactate, pyruvate and CO2, 15% in ethanol-insoluble fraction, 65% in neutral lipids, 75% in phospholipids, 80% in fatty acid moiety, 40% in deacylated fraction and 10% in the polysaccharide fractions. Refeeding the fasted animals or insulin treatment to the diabetic animals restored these depressed (14C)-recoveries to the normal levels. Fructose utilization was less than 10% of glucose utilization, but remained unaffected by fasting and diabetic states. In addition, pulmonary hexokinase enzyme activity was lowered significantly in fasting and diabetic animals, whereas fructokinase enzyme activity was not altered. Despite the low rate of fructose utilization, these results suggest that fructose may serve as an alternative substrate for pulmonary phospholipid synthesis when glucose utilization is significantly depressed.
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PMID:Nutritional and hormonal control of glucose and fructose utilization by lung. 390 22

In the practice of diagnosing occupational deafness resulting from noise effects of factors determining workers' hearing, such as living conditions, working conditions, nutritional and other habits, diseases and their therapy, are often neglected. Discussed in the paper are the significance and ototoxic effects of such factors as: aminoglycoside antibiotics, diuretics, salicylic acid derivatives, fenacetin, quinine, fluorine compounds, cytotoxic drugs, chemical compounds other than drugs (carbon monoxide, carbon disulphide, lead, organic solvents), ethyl alcohol, diseases (abdominal typhus, bacillary dysentery, diphtheria, brucellosis, epidemic parotiditis, poliomyelitis, rubella, aural shingles, syphilis, diabetes mellitus, chronic renopathies, hypothyroidism, serologic conflict, pigmentary retinitis). Exposure to intense noise is more and more frequently juxtaposed with the impact of the mentioned factors. If industrial physicians get aware of this association the prevention of deafness and reliability of treatment may be largely promoted.
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PMID:[Ototoxic factors requiring consideration in the diagnosis of occupational hearing loss]. 390 48

Specific binding sites for insulin have been identified and characterized for the human erythroleukemia cell line K-562. The binding of [125I]-insulin to the cells increased as a function of time, reaching a maximum at 20 min when incubation was performed at 37 degrees C. The binding of [125I]-insulin was dose-dependently inhibited by insulin or proinsulin. Scatchard plot of the binding data was curvilinear, and the number of insulin receptors was approximately 39,000. Insulin at concentrations of 0.05-10.0 ng/ml stimulated CO2 production and DNA and protein synthesis in K-562 cells in a dose-dependent manner, indicating that the insulin binding sites are functionally important in mediating these biochemical events induced by insulin. Maximal insulin responses were elicited at concentrations of less than 5 ng/ml, when (at most) 10% of the insulin receptors were occupied. After binding to the cells, [125I]-insulin was degraded in a time- and temperature-dependent manner. As reported for other types of cells, unlabeled insulin also downregulated insulin receptors in K-562 cells. When the cells were incubated with 1 X 10(-7) M unlabeled insulin for 24 h, the number of insulin receptors decreased by 50% without a change of affinity. K-562 cells may be useful in studying the role of insulin receptors in cell functions induced by insulin.
Diabetes 1985 Apr
PMID:Characteristics of insulin receptors and insulin action in human myelogenous leukemia cell line K-562. 391 4

A significant increase in CO2 production, reflecting carbohydrate oxidation and/or fat synthesis, is observed in normal subjects after the ingestion of glucose. The anatomic site(s) of this CO2 production has not yet been localized, although liver and muscle are logical considerations. To assess the contribution of skeletal muscle to this process, we measured whole-body and forearm CO2 flux in normal, postabsorptive subjects after the ingestion of 100 g of glucose and calculated their total muscle CO2 production. In the basal state, muscle accounted for 19% of total CO2 production, and, after glucose administration, muscle CO2 production did not change significantly. Thus, muscle is not the principal site of the observed increase in CO2 production.
Diabetes 1985 Oct
PMID:Role of muscle in CO2 production after oral glucose administration in man. 393 Mar 20

We recently examined three family members with acute carbon monoxide intoxication resulting from a single accidental exposure--a stepfather with a normal fundus, a mother with scattered superficial retinal hemorrhages, and her child with multiple large subinternal limiting membrane hemorrhages, peripapillary hemorrhages, severe venous tortuosity, and disc edema. All three had comparable carboxyhemoglobin levels and no evidence of hypertension, diabetes, or anemia. The different fundus presentations illustrated the variable clinical manifestations of carbon monoxide retinopathy. Early detection could prevent a lethal outcome.
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PMID:Carbon monoxide retinopathy. 397 78

It is known that dehydroascorbic acid (DHAA) produces a diabetogenic effect and its content in the blood increases in diabetes mellitus. It was previously established that the generation of reducing equivalents (RE) in the course of hexosemonophosphate shunt, CO2 production and SH-glutathione regeneration in erythrocytes with and without moderate and maximum oxidation load in vitro were not disturbed in diabetes. The authors have proposed a procedure to study blood and erythrocyte DHAA reductase activity in suspension in health and in insulin-dependent diabetes mellitus by means of redoxstatometry using a device of original design. A significant acceleration of RE transfer through the erythrocyte membrane was detected in diabetes. A lowered participation in this process of the AA in equilibrium DHAA "shuttle" system was recorded in the blood of patients with diabetes mellitus what was mostly expressed under the conditions of acidosis in vitro. Probably "shuttle" function in diabetes was provided by some other redox system which might be located in the plasma. The predominant functioning of this redox system and a decrease of DHAA reductase activity in diabetes resulted in the accumulation of DHAA in the blood of patients with type I diabetes mellitus.
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PMID:[Cause of dehydroascorbic acid accumulation in the blood of patients with insulin-dependent diabetes mellitus]. 398 93

300 consecutive laparoscopic tubal sterilizations performed from December 1971 to July 1973 are reviewed. Most patients were between the ages of 30 and 40 with a parity of 2 or 3. Other procedures were also carried out in 128 patients, including 89 D and C operations, 5 cervical biopsies, and 17 therapeutic abortions. In 2 cases, pregnancy had occurred with an IUD in situ. All sterilizations, except 2 for diabetes were done on an outpatient basis. General anesthesia was used. Carbon dioxide gas was injected for insufflation with gas pressure kept below 15 mm Hg. After anesthesia had been induced catheterization and bimanual examination were done and a self-retaining cannula placed in the uterus to later position the uterus and tubes. A 10-15 degree Trendelenberg position caused the bowel to fall upward out of the pelvis. Either a 1 or 2 puncture technique was satisfactory. Tubes were grasped, coagulated, and sectioned. After verification of hemostasis, the instruments were withdrawn and skin incisions closed with 5 sutures. Patients who had only sterilization usually went home about 3 hours after the operation. Little postoperative sedation was needed. All cases were successful with only minor complications. Improved designs in electrosurgical units are expected to minimize the risk of electrocoagulation injury.
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PMID:Laparoscopic tubal sterilization. 427 47

1. The overall metabolic changes in lactating mammary gland in alloxan-diabetic and anti-insulin-serum-treated rats were assessed by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into carbon dioxide and lipid, together with measurements of enzymes concerned with the pentose phosphate pathway and with citrate metabolism. 2. Alloxan-diabetes depressed the rate of formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose to approx. 10% of the control rate; this was partially reversed by addition of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.9 in the diabetic group and was restored to 14.3 in the presence of insulin in vitro. In keeping with these results it was shown that glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were significantly decreased in alloxan-diabetic rats. 3. Alloxan-diabetes depressed the decarboxylation and the oxidation of labelled pyruvate, but not the oxidation of labelled acetate. 4. The synthesis of lipid from specifically labelled glucose was greatly decreased, that from [2-(14)C]pyruvate was almost unchanged and that from [1-(14)C]acetate alone was increased in alloxandiabetic rats. However, the stimulation of lipid synthesis from acetate by glucose was small in the alloxan-diabetic rats compared with the controls. Insulin in vitro partially reversed all these effects. Both citrate-cleavage enzyme and acetate thiokinase activities were decreased in alloxan-diabetic rats. 5. Treatment of rats with anti-insulin serum depressed the formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose, but increased that from [6-(14)C]glucose. This was completely restored by the presence of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.8 in the anti-insulin-serum-treated group. There were no changes in the activity of glucose 6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but the hexokinase distribution changed and the content of the soluble fraction increased significantly. 6. The synthesis of lipid from specifically labelled glucose was depressed in anti-insulin-serum-treated rats; this effect was completely reversed by addition of insulin in vitro to the tissue slices.
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PMID:Effect of alloxan-diabetes and treatment with anti-insulin serum on pathways of glucose metabolism in lactating rat mammary gland. 569 42


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