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

Although the standard assays for reactive oxygen species have been based on the measurement of those released into the extracellular environment, the microbicidal capacity to the engulfed microorganisms is mainly dependent on those released into the intracellular environment, such as phagosomes. We studied intracellular oxidative activities of individual phagocytes by dichlorofluorescein (DCFH) oxidation assay to investigate the relationship between the reactive oxygen species released intracellularly and the impaired microbicidal capacity in diabetic patients. Time courses of intracellular production of hydrogen peroxide by polymorphonuclear leucocytes (PMNL) and monocytes were observed at the resting condition and after the stimulation with phorbol myristate acetate (PMA; 160 nM) by flow cytometry. Thirty-four patients with non-insulin-dependent diabetes mellitus (NIDDM) and 23 age-matched healthy volunteers were subjected to the studies. PMNL from patients with NIDDM showed a significantly decreased capacity to produce hydrogen peroxide after the stimulation (P less than 0.05 at 15 min, P less than 0.01 at 30 and 45 min). By contrast, intracellular hydrogen peroxide production by monocytes at the resting condition and an early stimulatory phase (8 min after the stimulation) was significantly (P less than 0.01) enhanced in patients with NIDDM compared with that in controls. Both the changes of intracellular hydrogen peroxide production observed in PMNL and monocytes from patients with NIDDM were in association with an increased haemoglobin Alc level in erythrocytes, but did not relate to total cholesterol and triglyceride levels in the serum. The possible mechanisms of these dissociated changes in hydrogen peroxide producing capacity of phagocytes from patients with NIDDM are discussed.
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PMID:Intracellular hydrogen peroxide production by peripheral phagocytes from diabetic patients. Dissociation between polymorphonuclear leucocytes and monocytes. 157 91

In nonobese diabetic (NOD) mice, T cells play a major role in mediating autoimmunity against pancreatic islet beta-cells. We and others previously reported that age-related alterations in the thymic and peripheral T cell repertoire and function occur in prediabetic NOD mice. To study the mechanism responsible for these T cell alterations, we examined whether a defect exists in the thymus of NOD mice at the level of TCR-mediated signaling after activation by Con A and anti-CD3. We found that thymocytes from NOD mice respond weakly to Con A- and anti-CD3-induced proliferation, compared with thymocytes from control BALB/c, BALB.B, (BALB.B x BALB.K)F1, C57BL/6, and nonobese non-diabetic mice. This defect correlates with the onset of insulitis, because it can be detected at 7 to 8 weeks of age, whereas younger mice displayed a normal T cell responsiveness. Thymic T cells from (NOD x BALB/c)F1 mice, which are insulitis- and diabetes-free, exhibit an intermediate stage of unresponsiveness. This T cell defect is not due to a difference in the level of CD3 and IL-2R expression by NOD and BALB/c thymocytes, and both NOD CD4+ CD8- and CD4- CD8+ mature thymic T cells respond poorly to Con A. BALB/c but not NOD thymic T cells respond to Con A in the presence of either BALB/c or NOD thymic APC, suggesting that the thymic T cell defect in NOD mice is intrinsic to NOD thymic T cells and is not due to an inability of NOD APC to provide a costimulatory signal. The defect can be partially reversed by the addition of rIL-2 to NOD thymocytes. To determine whether a defect in signal transduction mediates this NOD thymic T cell unresponsiveness, we tested whether these cells elevate their intracellular free Ca2+ ion concentration in response to Con A. An equivalent Con A-induced increase in Ca2+ ion concentration in both NOD and BALB/c thymocytes was observed, suggesting a normal coupling between the CD3 complex and phospholipase C in NOD thymocytes. In contrast to their low proliferative response to Con A or anti-CD3, NOD thymocytes respond normally (i.e., as do BALB/c thymocytes) to the combinations of PMA plus the Ca2+ ionophore ionomycin and PMA plus Con A but weakly to Con A plus ionomycin. Our data suggest that the age-related NOD thymocyte unresponsiveness to Con A and anti-CD3 results from a defect in the signaling pathway of T cell activation that occurs upstream of protein kinase C activation.
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PMID:Defective thymic T cell activation by concanavalin A and anti-CD3 in autoimmune nonobese diabetic mice. Evidence for thymic T cell anergy that correlates with the onset of insulitis. 182 15

In this study we evaluated the acceptability of using the first morning urine albumin concentration (FMAC) and the first morning urine albumin/creatinine (FMA/C) ratio as an indirect estimation of timed albumin excretion in order to screen for microalbuminuria in a large diabetic population. Urinary albumin excretion rate (AER) was determined in samples from 4-h urine collection in 99 type 1 diabetic patients aged 30 +/- 10 years with a mean duration of diabetes of 15 +/- 8 years. The results of timed albumin excretion were successively compared with single-void first morning samples. On the basis of AER, 46 patients were normoalbuminuric (AER less than 20 micrograms/min), 28 microalbuminuric (AER 20-200 micrograms/min), and 25 proteinuric (AER greater than 200 micrograms/min). The relationship of 4-h AER to FMAC and FMA/C ratio was highly significant (r = 0.96 and r = 0.98 respectively). High sensitivity and specificity were found when cut-offs of 20 micrograms/ml and 2.5 mg/mmol were selected for albumin concentration and albumin/creatinine ratio respectively to discriminate between normal and elevated albuminuria. It is concluded that the measurements of albumin concentration and albumin/creatinine ratio in first morning urine samples are highly representative of 4-h timed albumin excretion. Because of their sensitivity, specificity and simplicity to perform, the tests proposed might be used in routine diabetic care and as a screening test for microalbuminuria in type 1 (insulin-dependent) diabetic patients. The not negligible day-to-day variability in albumin excretion confirms the need of several measurements to establish the presence of abnormal levels of albuminuria above all in patients with borderline values and/or clinically unstable metabolic control.
Diabetes Res Clin Pract 1989 Nov 06
PMID:A screening test for microalbuminuria in type 1 (insulin-dependent) diabetes. 261 45

The study material comprised 60 patients treated at the Clinic of Ophthalmology PMA in Szczecin, in the years from 1981 to 1984 due to uveitis. In the patients routine laboratory examinations were performed and extended by additional ones in the direction of diseases being of rheumatoidal type, tuberculosis, toxoplasmosis, diabetes and focal infections. All the patients had rosette tests of E, EA, EAC prior to treatment and after 30 days of therapy. The patients were divided at random into 2 groups with 30 persons each. Apart from typical treatment for uveitis the group I was given the FIBS preparation. The clinical picture failed to reveal any significant differences between the groups of patients. It was observed that the count of lymphocytes T and B in the peripheral blood was disturbed. After the applied treatment changes were recorded in the count of lymphocytes T and B, the shiftings in the group of patients, having been treated with FIBS, were marked more distinctly, particularly in the count of lymphocytes T.
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PMID:[Evaluation of the effect of treatment with FIBS preparation on the clinical state and various parameters of the immune system in patients with uveitis]. 263 96

In 115 normal children (3 to 14 years old) and 143 children with insulin-dependent diabetes mellitus (6 to 15 years old), the urinary C-peptide immunoreactivity) was measured for evaluation of the pancreatic B cell function. The urinary C-peptide excretions during O-GTT corresponded to the change of serum C-peptide levels in normal children (n = 27) and the mean value of the excretions in younger children was significantly low. Age did not significantly affect basal serum C-peptide levels (ng/ml) and urinary C-peptide excretions (micrograms/h) before O-GTT, but significant differences in serum sigma C-peptide (ng/ml) and urinary C-peptide (micrograms/3 h) during O-GTT were noted between the younger group and the older group (p less than 0.01). In 39 normal children on an inactive routine, mean values of the 24 h urinary C-peptide for children aged from 3 to 6, 7 to 10 and from 11 to 14 years old, were 28.2 +/- 12.6 micrograms/day, 32.3 +/- 8.4 micrograms/day and 37.6 +/- 10.6 micrograms/day (mean +/- SD) respectively with significant differences according to age (younger group vs older group, p less than 0.05). The effects of daily routine on 24 h urinary C-peptide were studied in normal children. In children on an active routine, the C-peptide excretion was significantly less than in the same individuals on an inactive routine (26.9 +/- 9.9 micrograms/day vs 34.3 +/- 14.5 micrograms/day, p less than 0.01). In children with insulin-dependent diabetes mellitus, 24 h urinary C-peptide excretion was studied to evaluate residual pancreatic B cell function. Urinary C-peptide was measurable in 47 of the 143 diabetic children, suggesting that most of the pancreatic B cells had deteriorated in the other 96 patients. In the 96 patients without B cell function, the averages of daily dose of insulin and 24 h-U.glucose/TAG ratio were significantly higher than those in the 47 patients who had pancreatic B cell function estimated by measuring urinary C-peptide (p less than 0.001). In additional studies on the 43 diabetic children with residual pancreatic B cell function, who had had the disease for five years or less, the 24 h urinary C-peptide excretion (micrograms/day) correlated weakly but significantly with the duration of the disease (r = -0.28, p less than 0.05). Patients who had had the disease longer and who were controlled with larger doses of insulin had less of the 24 h urinary C-peptide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on urinary C-peptide excretion in normal children and children with insulin-dependent diabetes mellitus]. 265 21

In 150 newly detected type 2 diabetics the formation of macro- and microangiopathic complications during a 10-year control period was prospectively analysed, in order to demarcate possible factors of influence for the vascular prognosis under preventive points of view. Already at the time of manifestation there was with 34.3% an above average high prevalence of the coronary heart disease, particularly in the female sex. The prevalence of the coronary heart disease further increased to 49.7% in the course of diabetes and showed a correlation to the initial age, to the existence of overweight, hypertension, hyperlipoproteinaemia and nicotine consumption. The PMA was found comparatively more infrequent in the manifestation of diabetes (9.7%), but in the course of the disease highly significantly and independently of sex increased to 61.9%. The development of PMA was correlated with the age, the existence of hypertension and overweight. The frequency of retinopathy increased from initially 3.7% to 18.7%, the prevalence of nephropathy from 4.0% to 22.2%, without having found prognostic influence factors at the date of the diagnosis of diabetes.
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PMID:[Development of angiopathies in type 2 diabetes mellitus--results of a prospective 10 year study]. 324 47

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.
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PMID:Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. 660 15

Insulin might play a role in the hypertension occurring in insulin-resistant diabetes. In addition, insulin has recently been shown to potentiate norepinephrine (NE) induced vascular tone. We used ring segments of the rabbit facial artery mounted in a myograph to test the hypothesis that potentiation of NE-induced tone by insulin may be related to activation of protein kinase C (PKC) and tyrosine kinase (TK). NE-induced contractions in the presence of insulin (1 mU/mL) were 200% (NE 0.1 and 0.3 microM), 252% (NE 1 microM), and 129% (NE 3 microM) of control. Insulin (1 mU/mL) had no effect on NE (10 and 100 microM) induced contractions. The potentiation by insulin of NE-induced tone was not altered by endothelium removal and could be mimicked by phorbol-12-myristate-13-acetate (PMA, 0.1 microM). Histamine-induced contractions were not altered by insulin (1 mU/mL). Insulin potentiation of NE-induced tone was suppressed by pretreatment of the rabbit facial artery with the PKC inhibitor calphostin C (0.1 microM) or the TK inhibitor genistein (10 microM). 45Ca2+ influx due to NE (3 microM) did not change in the presence of insulin (1 mU/mL) or PMA (0.1 microM) despite a higher contractile response, so that wall force per unit of 45Ca2+ influx was increased by insulin (1 mU/mL) and PMA (0.1 microM). Calphostin C (0.1 microM) and genistein (10 microM) both prevented the increase in wall force per unit of 45Ca2+ influx due to insulin (1 mU/mL). Our study shows that insulin potentiates NE-induced tone through a TK- and PKC-dependent mechanism.
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PMID:Insulin potentiates norepinephrine-induced vascular tone by activation of protein kinase C and tyrosine kinase. 753 May 92

Extracellular fatty acids entering the hepatocyte are either esterified to cytosolic TAG or oxidized to ketone bodies. Very little is esterified and secreted directly in association with VLDL. Thus, even when extracellular fatty acids are available, the major, direct source of VLDL TAG is the cytosolic pool. The recruitment of cytosolic TAG for VLDL assembly involves lipolysis followed by re-esterification. At least 70% of the secreted TAG is derived via this route. Fatty acids released at this lipolytic step are utilized exclusively for VLDL TAG synthesis and are not available for ketogenesis. Substantially more cytosolic TAG undergoes lipolysis than is required to meet the needs of VLDL assembly. The remaining fatty acids are re-esterified and re-cycled to the cell cytosol. From a physiological viewpoint, the presence of this indirect route for VLDL TAG recruitment would provide a means of regulation of VLDL secretion which is independent of the plasma fatty acid concentration. In this respect, several pathophysiological conditions are known in which there is a negative association between plasma fatty acid concentration and the rate of VLDL secretion. These are: (a) insulin-dependent diabetes, (b) starvation, (c) fat-feeding. Lipolysis of cytosolic TAG and transfer of fatty acids into the ER lumen may provide a regulatory focus for the control of hepatic VLDL output.
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PMID:Intracellular triacylglycerol lipase: its role in the assembly of hepatic very-low-density lipoprotein (VLDL). 757 43

Inhibition of Na+,K(+)-ATPase activity by hyperglycemia could be an important etiological factor of chronic complications in diabetic patients. The biochemical mechanism underlying hyperglycemia's inhibitory effects has been thought to involve the alteration of the protein kinase C (PKC) pathway since agonists of PKC can normalize hyperglycemia-induced inhibition of Na+,K(+)-ATPase activity. Paradoxically, elevated glucose levels and diabetes have been shown to increase PKC activities in vascular cells. The present study tested the hypothesis that the inhibition of Na+,K(+)-ATPase activity is mediated by the sequential activation of PKC and cytosolic phospholipase A2 (cPLA2). In cultured rat vascular smooth muscle cells (VSMC), increasing glucose levels in the medium from 5.5 to 22 mM elevated cPLA2 activity and increased [3H]arachidonic acid release and PGE2 production by 2.3-, 1.7- and 2-fold, respectively. Similar increases in cPLA2 activity were also induced by elevated glucose levels in human VSMC and rat capillary endothelial cells. The activation of cPLA2 was mediated by PKC since the increases in cPLA2 phosphorylation and enzymatic activity were inhibited by the PKC inhibitor GFX. In contrast, elevation of glucose levels decreased Na+,K(+)-ATPase activity as measured by ouabain-sensitive 86Rb uptake by twofold in rat VSMC. Surprisingly, both PMA, a PKC agonist, and GFX, a PKC inhibitor, were able to prevent glucose-induced decreases in 86Rb uptake. Further, the PLA2 inhibitor AACOCF3 abolished both glucose-induced activation of cPLA2 and the decrease in 86Rb uptake. These data indicated that hyperglycemia is inhibiting Na+,K(+)-ATPase activity by the sequential activation of PKC and cPLA2, resulting in the liberation of arachidonic acid and increased the production of PGE2, which are known inhibitors of Na+,K(+)-ATPase.
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PMID:Identification of the mechanism for the inhibition of Na+,K(+)-adenosine triphosphatase by hyperglycemia involving activation of protein kinase C and cytosolic phospholipase A2. 763 66


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