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)

A rabbit polyclonal antibody to purified ox kidney branched-chain oxo acid dehydrogenase complex was shown by a variety of techniques to be an antibody to the E2 (acyltransferase) component. Rocket immunoelectrophoresis showed that the antibody does not discriminate between phosphorylated (inactive) or dephosphorylated (active) complex, and the same technique is used to assay total branched-chain complex (sum of active and inactive forms) in rat liver and heart mitochondrial extracts. The values obtained in normal rats fed on normal diet were comparable with those obtained by spectrophotometric assay of the holocomplex reaction after conversion of inactive complex into active complex. The values obtained in liver mitochondria from rats fed on 0%-casein diet or starved for 48 h were comparable with those in rats fed on normal diet, whereas earlier studies using spectrophotometric assay had shown substantial decreases in rats fed on 0%-casein diet or starved for 48 h. It has been shown that conversion of inactive complex into active complex requires prolonged incubation (120 min) in the presence of ketoleucine (4-methyl-2-oxopentanoate; to inhibit branched-chain oxo acid dehydrogenase kinase) to effect complete conversion in mitochondria from rats fed on 0%-casein diet, or starved for 48 h, or made diabetic with alloxan. By this technique, total activity of the complex in rat liver mitochondria was unaffected by diet or diabetes. The effects of diet and diabetes to decrease the activity of branched-chain complex in rat liver are therefore apparently mediated wholly through inactivation of the complex by phosphorylation.
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PMID:Rat tissue concentrations of branched-chain 2-oxo acid dehydrogenase complex. Re-evaluation by immunoassay and bioassay. 374

Starvation, diabetes and insulin did not alter the concentration of casein kinases in rat liver cytosol. However, the Km for casein of casein kinase 2 from diabetic rats was about 2-fold lower than that from control animals. Administration of insulin to control rats did not alter this parameter, but increased the Km for casein of casein kinase 2 in diabetic rats. Starvation did not affect the kinetic constants of casein kinases. The effect of diabetes on casein kinase 2 persisted after partial purification of the enzyme by glycerol-density-gradient centrifugation and affected also its activity on other protein substrates such as phosvitin, high-mobility-group protein 14 and glycogen synthase. The results indicate that rat liver cytosol casein kinase 2 is under physiological control.
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PMID:Effect of starvation, diabetes and insulin on the casein kinase 2 from rat liver cytosol. 388 88

In conscious dogs intravenously infused somatostatin (3.3 mug per min for 1 h) caused prompt and sustained declines in mean plasma insulin and glucagon, even during alanine infusion and intraduodenal casein hydrolysate feeding; plasma glucose declined, but not significantly. 6.7 mug per min of somatostatin significantly lowered pancreatoduodenal vein glucagon and insulin within 2.5 min and profoundly suppressed their secretion throughout the infusion. Consistent bihormonal suppression occurred at rates as low as 24 ng per kg per min, but was variable at 12 and 2.4 ng per kg per min. When somatostatin-induced (3.3 mug per min) hypoglucagonemia was corrected by exogenous glucagon, hyperglycemia occurred. In dogs with long-standing insulin-requiring alloxan diabetes 3.3 mug per min of somatostatin suppressed glucagon to 55 pg per ml throughout the 30-min infusion and lowered glucose by 36.4+/-6.1 mg per dl, about 1 mg per dl per min. Glucagon suppression was maintained despite alanine infusion, and glucose, which rose 29 mg per dl during alanine infusion without somatostatin, declined 58 mg per dl in the somatostatin-treated diabetic dogs despite alanine. Continuous infusion of somatostatin for 24 h in five insulin-requiring alloxan-diabetic dogs suppressed glucagon and lowered glucose significantly, usually to below normal. It is concluded that in normal dogs pharmacologic doses of somatostatin virtually abolish insulin and glucagon secretion in the basal state and during hyperaminoacidemia. Hyperglycemia occurs during somatostatin-induced insulin lack only if hypoglucagonemia is corrected. Somatostatin suppresses glucagon in diabetic dogs and lowers their plasma glucose approximately 1 mg per dl per min, even when the gluconeogenic substrate alanine is abundant. Glucagon suppression can be maintained for several hours in such dogs and hyperglycemia is thereby reduced.
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PMID:Somatostatin-induced changes in insulin and glucagon secretion in normal and diabetic dogs. 443 39

The total activities (sum of active and inactive forms) of branched-chain 2-oxo acid dehydrogenase complex in tissues of normal rats fed on a standard diet were (unit/g wet wt.): liver, 0.82; kidney, 0.77; heart, 0.57; hindlimb skeletal muscles, 0.034. Total activity was decreased in liver by 9%- or 0%-casein diets and by 48 h starvation, but not by alloxan-diabetes. Total activities were unchanged in kidney and heart. The amount of active form of the complex (in unit/g wet wt. and as % of total) in tissues of normal rats fed on standard diet was: liver, 0.45, 55%; kidney, 0.55, 71%; heart, 0.03, 5%; skeletal muscle less than 0.007, less than 20% (below lower limit of assay). The concentration of the active form of the complex was decreased in liver and kidney, but not in heart, by low-protein diets, 48 h starvation and alloxan-diabetes. In heart muscle alloxan-diabetes increased the concentration of active complex. The concentration of activator protein (which activates phosphorylated complex without dephosphorylation) in liver and kidney was decreased by 70-90% by low-protein diets and 48 h starvation. Alloxan-diabetes decreased activator protein in liver, but not in kidney. Evidence is given that in tissues of rats fed on a normal diet approx. 70% of whole-body active branched chain complex is in the liver and that the major change in activity occasioned by low-protein diets is also in the liver.
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PMID:Effects of diet and of alloxan-diabetes on the activity of branched-chain 2-oxo acid dehydrogenase complex and of activator protein in rat tissues. 648 71

Diabetes in rats inhibits the migration of neutrophils into the healing gingival crevice, an effect associated with impaired in vitro neutrophil chemotactic activity. We recently described the in vivo response of human and rat crevicular neutrophils to a chemotactic challenge and used this assay in the present study on streptozotocin-induced diabetic rats. Optimal concentrations of two chemotactic agents, casein (0.2 mul, 2 mg/ml) or N-formylmethionylleucylphenylalanine (0.2 mul, 10(-4) M), were placed into the gingival crevices of control and diabetic rats (time zero) after the resting neutrophil count was measured. After a 15-min delay, the neutrophil counts and gingival crevicular fluid flow were assessed every 5 min for another 0.5 h. The control rats (n = 14) showed an increase in neutrophil counts which reached maximum levels 30 min after the N-formylmethionylleucylphenylalanine challenge ("peak" neutrophil response) and decreased dramatically 5 min later. Diabetes of 4 days (n = 4), 14 days (n = 8), and 20 days (n = 5) duration reduced the peak neutrophil response 45, 66, and 71%, respectively. Casein produced the same response as N-formylmethionylleucylphenylalanine in control rats. Uncontrolled diabetes of 20 days duration reduced the peak neutrophil response to casein by 83%; diabetics administered insulin on a daily basis showed a reduction of only 34%. The pattern of change in gingival crevicular fluid flow in response to chemoattractants paralleled the neutrophil response. The chemotactic activity of peritoneal neutrophils was assessed in vitro with the agarose gel technique and was found to be correlated (r = 0.84; P < 0.01) with the in vivo chemotactic response in the same rats. If the same in vivo defect is observed in humans with diabetes (or with other systemic diseases associated with leukocyte dysfunction), this test could be useful diagnostically to rapidly assess neutrophil chemotaxis in lieu of in vitro assays and to identify patients who are unusually susceptible to aggressive periodontal disease.
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PMID:In vivo crevicular leukocyte response to a chemotactic challenge: inhibition by experimental diabetes. 675 17

Male weanling rats were fed one of three diets for 46 days. The diets were control, a 4% casein-containing and a 4% casein + 0.7% cysteine diets. On day 47, the rats were injected with alloxan (40 mg/kg body weight) via the tail vein and frequencies of alloxan-induced diabetes were appraised on days 55-57 by measurement of blood glucose, urine output, water intake and food intake. Alloxan was almost ineffective in producing diabetes in the two low-protein groups (frequencies of diabetes = 0/11 and 3/11 for the 4% casein diets without and with cysteine, respectively) but was highly effective in the control group (100% diabetogenesis). The decreased diabetogenicity of low-protein diets was not due to decreased food intake. All the animals fed control diet in amounts which matched the intake of protein-malnourished animals became diabetic when alloxan was administered. These data suggest a defect in the alloxan-glucose recognition site on beta cells of protein malnourished rats.
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PMID:Lack of diabetogenic effect of alloxan in protein-calorie malnourished rats. 676 15

In New Zealand rabbits a single intravenous injection of streptozotocin (STZ 65 mg/kg) elevated the levels of blood sugar to 340 mg percent, which was associated with glycolysis, ureamia, hypercholesterolemia, hypertriglyceridemia and loss of body weight. Oral administration of jambolan seed (1 g/kg) in casein diet significantly lowered the elevated postmeal (1 1/2 hr after) values of blood sugar, cholesterol, FFA and triglyceride down to levels comparable to phenformin. Jambolan seed treatment failed to check ureamia. Weight loss was checked by phenformin and jambolan seed but the gain was not equivalent to that recorded in nondiabetic control. Like phenformin, jambolan seed too failed to control glycogenolysis in STZ-induced diabetes.
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PMID:Effects of jambolan seed treatment on blood sugar, lipids and urea in streptozotocin induced diabetes in rabbits. 688 26

Weanling C57BL/KsJ homozygous diabetic (db/db) and normal littermate (+/+ or +/db) mice were maintained for 5 mon on isocaloric diets containing either 60% sucrose, 23% casein, 8% corn oil (diet C) or 0% sucrose, 83% casein, 8% corn oil (diet B). Diabetic homozygotes consumed more diet C than normals, but ate control amounts of diet B. Diabetic mice fed diet C exhibited 57% mortality between 4 or 5 mo of age. All diabetic mutants fed the carbohydrate-free diet B appeared healthy at 6 mo of age; mutant females were normoglycemic and mutant males were only moderately hyperglycemic. Histological examination of pancreatic islets confirmed the absence of islet degeneration. In diet B maintained mutants, increased carcass fat composition, plasma and pancreatic content of insulin and glucagon, and thymidine incorporation into islets, all established that the db gene was being fully expressed. These results indicate that dietary protein stimulates islet growth and function in db/db mice, while high levels of refined carbohydrate in the diet predispose islet beta cells to undefined changes that culminate in necrosis. Restricting mutants' intake of a carbohydrate-containing diet to one-half the caloric intake of normal mice failed to block onset of beta cell necrosis. Thus, dietary composition rather than total caloric intake appears to be critical in the induction of islet necrosis and atrophy in this animal model of genetically transmitted diabetes.
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PMID:Dietary control of pathogenesis in C57BL/KsJ db/db diabetes mice. 701 72

Experiments were designed to study the chemotaxis and phagocytic functions of mouse peritoneal exudate macrophages from normal and chronic diabetic mice. There was no difference in the total number of white blood cells (WBC's), or the total number of any one type of leukocyte (i.e., macrophage, neutrophil) migrating into the casein-induced peritoneal exudate of normal and diabetic mice. In vitro phagocytosis of heat-killed Candida albicans by peritoneal induced macrophages was also similar in both of these groups of mice. No correlation between the percent phagocytosis and blood glucose level within each group was observed. Therefore, the attenuated humoral and cellular immune response which has been previously observed in diabetes cannot be attributed to defects in chemotaxis or phagocytosis as studied using mouse peritoneal macrophages.
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PMID:Phagocytosis and chemotaxis of macrophages from normal and diabetic mice. 701 47

The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from the healthy individuals. Phagocytosis of Candida albicans was decreased in the monocytes from the patients, whereas pinocytosis of acridine and phagocytosis of latex and sheep red blood cells were normal. The chemotactic response towards casein was enhanced. The possible consequences of these findings for the elucidation of concomitant infections in diabetic patients are discussed.
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PMID:Monocyte functions in diabetes mellitus. 704 41


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