Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines, in particular IL-1, released mainly by infiltrating macrophages, can be one of the key mediators of immune-induced beta-cell destruction in IDDM. IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets. In addition, the cytokine shows clear cytotoxic effects leading to beta-cell death. The proposed mechanisms of action of IL-1 after binding to the beta-cell receptors are varied. Concerning the cytotoxic effects of the cytokine, the role of oxygen free radicals, mainly derived from arachidonate metabolism (see Fig. 1) is clear, and possibly potentiated by a cytosolic Na(+)-mediated alkalinization of the beta-cell exposed to the cytokine. In fact, an increased influx of Na+ may explain some of the cytotoxicity since it results in concomitant water uptake leading to swelling of the endoplasmic reticulum. NO formation also seems to be related to the cytokine-induced cytotoxicity since inhibition of the NO synthase abolishes the effects of the cytokine (see Fig. 1). In relation to the inhibitory effects of the cytokine on the beta-cell, different studies point toward almost all known second messenger systems already described for several hormones, such as cAMP formation, increased phospholipase C activity, changes in cytosolic Ca++, and altered gene transcription (see Fig. 1). Of particular interest is the protease activation associated with IL-1 (a serine protease) that seems to be clearly connected with the effects of the cytokine upon the beta-cell. In conclusion, the different studies devoted to the problem of IL-1 signal transduction on the beta-cell seem to indicate that the action of the cytokine on the pancreatic insulin-secreting cells is not associated with an individual second messenger system but rather seems to be related to a plurifactorial transduction system.
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PMID:Interleukin-1 and beta-cell function: more than one second messenger? 142 86

The purpose of this study was to evaluate the cardiorespiratory and metabolic response to exercise in 33 children, aged 9 to 15 years, affected by type I diabetes mellitus, in comparison with 47 age-, sex-, weight-, and height-matched healthy children. All diabetic children were on a mixed split-dose insulin regimen, consisting of both regular and long-acting insulin in the morning and evening. The last insulin injection was administered on average 6 hours before the test. The mean duration of diabetes mellitus was 5.0 +/- 3.1 years. The metabolic control was evaluated on the basis of HbA1 levels (mean, 8.9 +/- 1.8%). Pulmonary function tests and progressive exercise tests on the treadmill were performed. Gas exchange, ventilation, and heart rate (HR) were monitored during the tests. The O2 pulse (VO2/HR) was calculated. There was no difference in the baseline oxygen uptake (VO2) between the diabetic children and the control group. VO2 peak was significantly lower (P less than 0.01) in the diabetic adolescents (41.2 +/- 5.9 mL/min/kg) compared to control subjects (46.3 +/- 9.6 mL/min/kg) and it was achieved at an earlier (P less than 0.01) time of run (7.5 +/- 1.8 vs. 9.1 +/- 2.8 min). Anaerobic threshold and minute ventilation were similar in the two groups. The O2 pulse throughout the test was significantly lower (ANOVA, P less than 0.001) in the diabetic group compared to the controls. No differences were found in resting and post-exercise spirometric values. In conclusion, our study shows that well-controlled diabetic adolescents have a reduced working capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gas exchange during exercise in diabetic children. 143 29

A study was made of the interrelationship of myocardial perfusion with physical working capacity in different types of DM (with the duration of disease from 4 to 8 years without clinical signs of circulatory insufficiency). Rated physical exercise testing in 12 patients with insulin dependent diabetes and 27 patients with noninsulin dependent diabetes as well as in 40 healthy subjects has shown a GTT decrease in diabetes mellitus irrespective of patient's age, sex and body mass to be more marked in noninsulin dependent type and to be closely related to disturbed oxygen supply of the heart and a lowered myocardial reserve. Bicycle ergometric testing combined with 201Tl scintigraphy in 20 patients has shown disorder of perfusion in all the patients irrespective of a diabetes type and duration of disease. Insulin dependent diabetes mellitus was characterized by stable perfusion defects resulting from metabolic derangements, and noninsulin dependent diabetes mellitus was characterized by a decrease in the level of a maximum Tl uptake by the myocardium and transient perfusion defects of ischemic type.
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PMID:[Physical working capacity and myocardial perfusion in patients with diabetes mellitus]. 178 5

The development of IDDM results from the destruction of pancreatic beta cells. Genetic factors, various immune system alterations, and environmental factors have been studied as the possible causes of IDDM. The concordance rate for developing IDDM between monozygotic twins approaches 50%, suggesting that genetic factors are necessary, but nongenetic factors such as various immune system alterations and environmental factors also influence the clinical expression of genetic susceptibility. Environmental factors (e.g., viruses, chemicals, and diet) affecting the induction of diabetes may act as primary injurious agents which damage pancreatic beta cells or as triggering agents of autoimmunity. Certain viruses including EMC-D and Mengo virus 2T can directly infect pancreatic beta cells and replicate in the cells. The replication of viruses in the beta cells results in the destruction of the cells within 3 days, and the infected mice develop a diabeteslike syndrome in 3-4 days without the involvement of autoimmunity. In contrast, rubella virus appears to be somewhat weakly associated with autoimmune IDDM in hamsters. In addition, endogenous retrovirus expressed in pancreatic beta cells is clearly associated with the development of insulitis and diabetes in NOD mice. In man, there appears to be no correlation between the detection of islet cell autoantibodies and anti-Coxsackie B viral antibodies in newly diagnosed IDDM. In contrast, persistent infection of CMV and rubella virus appears to be associated with the presence of autoantibodies in newly diagnosed IDDM patients. It is particularly noteworthy that human CMV can induce islet cell autoantibodies that react specifically with a 38 kDa islet cell protein which may represent islet cell-specific antigens in a proportion of CMV-associated IDDM cases. These observations suggest that the association of diabetes with Coxsackie B viruses might be due to cytolytic infection of the beta cells with no link to autoimmunity, while both rubella virus and CMV are probably associated with autoimmune IDDM. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, Vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. Possible mechanisms for beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and a consequent increase in the activity of poly-ADP-ribose synthetase, an enzyme depleting nicotinamide adenine dinucleotide in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of viruses and environmental factors in the induction of diabetes. 207 86

The respiratory burst of polymorphonuclear leukocytes was investigated in 24 children with insulin dependent diabetes mellitus and 24 healthy controls. This oxygen dependent, membrane associated process generates a number of toxic oxygen metabolites which are implicated in the pathogenesis of endothelial damage. The activity of polymorphonuclear leukocytes was studied in terms of luminol amplified chemiluminescence. It was found that the resting luminol amplified chemiluminescence activity of isolated polymorphonuclear leukocytes from diabetic children was significantly higher than that of controls (342,000 +/- 174,000 cpm vs. 165,000 +/- 82,000 cpm, p less than 0.01). The addition of respiratory burst inhibitors caused a significant reduction of basal chemiluminescence (greater than 80%). When the ratio of phorbol myristate acetate stimulated activity to basal activity was calculated and used as an activation index, it was found to be significantly reduced in diabetics relative to controls (4.29 +/- 2.46 vs. 8.34 +/- 3.21, p less than 0.01). These observations suggest that increased release of toxic oxygen metabolites from polymorphonuclear leukocytes in diabetic subjects may play a role in the development of diabetic angiopathies.
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PMID:Alterations of the respiratory burst of polymorphonuclear leukocytes from diabetic children. A chemiluminescence study. 216 90

Using a recently designed combined laser Doppler/transcutaneous oxygen probe postocclusive reactive hyperemia response was investigated in 10 healthy subjects and 33 patients with type I diabetes mellitus. From the foot dorsum sensing site simultaneous recordings of the red cell flux of the superficial skin microvasculature and cutaneous PO2 were obtained at identical measuring position and conditions. Whereas cutaneous PO2 response exhibited an uniform monophasic curve with a significantly reduced percentage increase of PO2 in short-term (p less than 0.05) and in long-term type I diabetic patients (p less than 0.001), four different laser Doppler hyperemic flux patterns were observed. Hyperemia types A and B were biphasic, type C had only a monophasic course. Apparently in type C the initial fast component of the myogenic response is missing; in type D no increase in flux or PO2 could be measured. Comparison of prevalence of these hyperemia types showed a significantly (p less than 0.05) higher prevalence of the monophasic or even absent hyperemic response in type I diabetes. The reduction in viscoelastic properties of the small arteries and arterioles in patients with type I diabetes may account for these changes which is most likely cofactor in the pathogenesis of diabetic microangiopathy.
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PMID:Cutaneous reactive hyperemia in short-term and long-term type I diabetes--continuous monitoring by a combined laser Doppler and transcutaneous oxygen probe. 218 59

1,5-Anhydroglucitol is a six-carbon chain monosaccharide in C1-chair conformation with an oxygen ring in pyran position. The compound is a component of normal human blood serum. The concentration in serum fluctuates within a narrow range in a normal population. Very low serum concentrations are found in patients with diabetes mellitus. In insulin-dependent (type 1) diabetes with a long history of disease the concentration of 1,5-anhydroglucitol remains low in spite of improvement of glycaemic control by intensification of treatment, whereas in non-insulin dependent (type 2) diabetes the concentration gradually increases towards normal levels concomitantly with improvement in glycaemic control. The serum 1,5-anhydroglucitol concentration may be useful as an indicator of glycaemic control in patients with non-insulin dependent diabetes. Urinary excretion of 1,5-anhydroglucitol in normal subjects is very low inferring that the compound is efficiently reabsorbed by tubular cells. During glucosuria, induced by glucose tolerance test in human or streptozotocin administration in rats the 1,5-anhydroglucitol excretion is temporarily increased, which may be attributable to a competition between 1,5-anhydroglucitol and glucose for renal tubular transporters. Data so far obtained indicate that 1,5-anhydroglucitol may be either actively or passively transported through the cell membrane, depending on the cell type. Gas-liquid chromatography is the method of choice in the measurement of the low concentrations of 1,5-anhydroglucitol present in biological samples.
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PMID:1,5-Anhydro-D-glucitol--a novel type of sugar in the human organism. 224 84

The diabetogenic action of alloxan is known to be attenuated by several oxygen radical scavengers. The present study was conducted to see if probucol, a drug with strong free radical scavenger action, can reduce pancreatic B-cell damage induced by alloxan in male Wistar rats. After 2 weeks of a 1% probucol diet, 50 mg/kg alloxan was intravenously injected in rats (group PA, n = 34). Urine glucose of most of the injected rats not pretreated with probucol (group A, n = 22) was positive, while more than half of the rats of group PA failed to show urine glucose. The blood glucose level in group PA was significantly lower than that in group A (326 +/- 25 vs. 487 +/- 28 mg/dl, P less than 0.001). Histological examination revealed that most of the pancreatic islets of group A were degranulated, whereas a lot of islets remained unaffected in group PA. Thus, the in vivo diabetogenic action of alloxan was reduced by pretreatment with probucol, although the effect was incomplete. This effect can be explained by probucol's strong free radical scavenger action. Since accumulation of free radicals can be an initial step of B-cell damage in animal models of type 1 (insulin-dependent) diabetes, the drug can be useful for the prevention of type 1 diabetes with its long-term clinical history of safety.
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PMID:Protective effect of probucol on alloxan diabetes in rats. 269 32

Blood rheological properties and oxygen metabolism were investigated in 50 patients with type I insulin dependent diabetes mellitus. Metabolic and morphological phases of the blood hyperviscosity syndrome were defined in relation to the nature of hemorheological disturbances. Oxygen metabolic disturbances were of unidirectional type manifesting themselves in a decrease in tissue oxygenation and the development of tissue hypoxia. Such disturbances of rheological properties and oxygen metabolism caused the development and progression of diabetic microangiopathies. Therefore pharmacological correction of hemorheological disturbances is a reserve method of therapy of patients with diabetes mellitus.
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PMID:[Blood hyperviscosity syndrome in type I diabetes mellitus]. 276 62

Hormonal studies of pituitary-testicular function in insulin-dependent diabetes mellitus were examined at rest and during moderate exercise to assess whether diabetes per se caused abnormalities of nocturnal penile tumescence and androgen function in men with normal sexual function. The present study compared 10 healthy men and eight men with Type I diabetes mellitus in whom normal sexual function was determined by clinical history. Urinary gonadotropin excretion, semen analysis and diurnal variation of serum glucose, prolactin, testosterone and free testosterone were determined in both groups. In addition, the serum levels of testosterone, free testosterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured at rest, during 45 minutes of exercise on a bicycle ergometer at 50% of the subjects previously determined maximal oxygen uptake (VO2 max) and during a 30-minute recovery period. Nocturnal penile tumescence and parameters of semen analysis were similar in both groups. Urinary FSH excretion and serum FSH were higher (P less than or equal to 0.01) in the diabetic subjects while urinary LH excretion was similar. Diurnal variation of serum prolactin, testosterone and free testosterone were similar in both groups. Exercise produced a significant (P less than or equal to 0.01) increase in maximal free and total testosterone in both groups without changes in serum FSH or LH. Prolactin increased significantly (P less than or equal to 0.01) during exercise in the diabetic group only. We conclude that, for the most part, the pituitary-testicular axis and nocturnal penile tumescence under basal conditions and the pituitary-testicular axis during moderate exercise are similar in healthy males and insulin-dependent diabetic males with normal sexual function.
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PMID:The pituitary-testicular axis at rest and during moderate exercise in males with diabetes mellitus and normal sexual function. 313 19


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