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

Werner's syndrome is a rare inheritated disorder characterized by accelerated aging and is often accompanied by diabetes mellitus or impaired glucose tolerance. Previous reports suggest that insulin resistance is involved in the development of diabetes associated with Werner's syndrome. In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. The patients were hospitalized for the duration of the study. During a pretreatment period lasting 8 weeks the patients received a controlled diet, however, their previous treatment was unchanged. Throughout the 4-week treatment period, each subject's blood glucose level was measured 7 times each day (07:30, 10:00, 11:30, 14:00, 17:30, 20:00, 22:00) for 1 week at 8, 4, and 1 week before treatment and at 2 and 4 weeks after treatment. To assess insulin action, the euglycemic glucose clamp technique was performed in these subjects at insulin infusion rates of 20, 120 and 400 mU/kg/min before and after 4 weeks of treatment. After 4 weeks of treatment with CS-045, the mean blood glucose level at each time point measured in this study was markedly lower compared to the corresponding pretreatment level.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1994 Jul
PMID:Increased insulin responsiveness after CS-045 treatment in diabetes associated with Werner's syndrome. 798 48

Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections. The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease is rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant recipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine. 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD strain). Animals were protected to 90% against challenge infection. 2. Inactivated whole vaccine. We used beta-propiolactone to inactive Coxsackie B3 virus. 74% of the animals survived if the vaccine was prepared with Quil A matrix as adjuvant. The neutralisation antibody titres varied from < 5 to 320. By comparison aluminium hydroxide (p = 0.06) and Freund's adjuvant were inferior (p < 0.01). 3. Subunit vaccines. We have previously used the ISCOM (immunostimulatory complex) technology to produce a Coxsackie B3 subunit vaccine. High levels of neutralizing antibodies were obtained (512)-comparable to natural infection. All animals survived challenge infection after two booster doses with 16 nanogram of the ISCOM preparation. Limiting for this technique was the availability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be obtainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutralisation antibody titre.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis. 839 Jul 13

The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine-->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with Ki = 2.8 +/- 0.5 and 4.2 +/- 0.7 microM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.
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PMID:(+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria. 842 95

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N-acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H2O2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.
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PMID:Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation. 940 71

Acute magnesium (Mg) infusion decreases patathyroid hormone (PTH) secretion. However, the effect of chronic hypermagnesemia on PTH levels in dialysis patients is not well established. We studied 110 hemodialysis patients (mean age, 55 +/- 14 years; time on dialysis, 35 +/- 28 months) not receiving vitamin D and undergoing dialysis with an Mg dialysate concentration of 1.2 mg/dL. The primary phosphate binder was calcium carbonate, and 43% of the patients also needed aluminum hydroxide. During a 6-month period, calcium (Ca), phosphorus (P), and total serum Mg were measured every 2 months; intact PTH and aluminum (Al) were measured every 6 months. The mean value of each parameter was computed. Hypermagnesemia (serum Mg > 2.47 mg/dL) was observed in 73% of the patients. Mg and Ca were inversely correlated with PTH levels (r = -0.48; P < 0.001 and r = -0.21; P < 0.05, respectively). After adjusting for Ca and P (partial correlation analysis), Mg and PTH were inversely correlated (r = -0.58; P < 0.001). A stepwise multiple regression analysis showed that PTH levels were predicted by Mg (P < 0.001), alkaline phosphatase (P < 0.01), and P levels (P< 0.05; multiple R = 0.57; P < 0.001), whereas Ca level, sex (dummy variable), diabetes (dummy variable), time on dialysis, and Al level were not predictive. Patients with inadequately low PTH levels (relative hypoparathyroidism, PTH < 120 pg/mL; n = 52) showed greater serum Mg concentrations than the rest (n = 58; 3.01 +/- 0.33 v 2.63 +/- 0.38 mg/dL; P < 0.001). In conclusion, serum Mg concentrations in dialysis patients are independently associated with PTH levels, suggesting that chronic hypermagnesemia may decrease PTH secretion and/or synthesis. In addition, chronic hypermagnesemia of dialysis patients may have a role in the pathogenesis of adynamic bone disease.
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PMID:Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients. 1040 Oct 14

To test the hypothesis that magnesium depletion might be of importance for the development of vascular complications in diabetes mellitus we performed a randomized, double-blind, placebo-controlled study during 12 months with 20-30 mmol/day of oral magnesium hydroxide in 28 type 1 diabetic patients. Urinary albumin excretion, Cr-EDTA-clearance and certain blood cardiovascular risk factors were measured. At the end of the study there were no significant differences of these parameters between the two groups, except that serum triglyceride values increased in three magnesium treated patients who either showed an increase in blood glycosylated hemoglobin values or body weight during the study.
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PMID:Magnesium therapy in type 1 diabetes. A double blind study concerning the effects on kidney function and serum lipid levels. 1042 7

Central nervous system damage in diabetes is caused by both cerebral atherosclerosis and the detrimental effect of chronic hyperglycaemia on nervous tissue. Hyperglycaemia is the primer of a series of cascade reactions causing overproduction of free radicals. There is increasing evidence that these reactive molecules contribute to neuronal tissue damage. Dehydroepiandrosterone (DHEA) has been reported to possess antioxidant properties. This study evaluates the oxidative status in the synaptosomal fraction isolated from the brain of streptozotocin-treated rats and the antioxidant effect of DHEA treatment on diabetic rats. Hydroxyl radical generation, hydrogen peroxide content, and the level of the reactive oxygen species was increased (P<0.05) in synaptosomes isolated from streptozotocin-treated rats. The derangement of the oxidative status was confirmed by a low level of reduced glutathione and alpha-tocopherol. DHEA treatment (4 mg per day for 3 weeks, per os) protected the synaptosomes against oxidative damage: synaptosomes from diabetic DHEA-treated rats showed a significant decrease in reactive species (P<0.05) and in the formation of end products of lipid peroxidation, evaluated in terms of fluorescent chromolipid (P<0.01). Moreover, DHEA treatment restored the unsaturated fatty acid content of the membrane and the reduced glutathione and alpha-tocopherol levels to normal levels and restored membrane NaK-ATPase activity close to control levels. The results demonstrate that DHEA supplementation greatly reduces oxidative damage in synaptosomes isolated from diabetic rats and suggest that this neurosteroid may participate in protecting the integrity of synaptic membranes against hyperglycaemia-induced damage.
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PMID:Oxidative derangement in rat synaptosomes induced by hyperglycaemia: restorative effect of dehydroepiandrosterone treatment. 1085 34

The antidiabetic effects of Ficus carica leaf extracts have been reported previously. From the aqueous decoction of fig leaves, after treatment with HCI, centrifuging, treatment with sodium hydroxide (NaOH) and extraction with chloroform (CHCl3), the administration of the organic phase rats with streptozotocin-induced diabetes led to a decline in the levels of total cholesterol and an decrease in the total cholesterol/HDL cholesterol ratio (with respect to the control group), together with a reduction of the hyperglycaemia.
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PMID:A chloroform extract obtained from a decoction of Ficus carica leaves improves the cholesterolaemic status of rats with streptozotocin-induced diabetes. 1103 50

4-Hydroxy-2-nonenal (HNE) is one of the major lipid peroxidation products with cytotoxic and mutagenic activity. It further reacts with protein residues such as histidine to generate stable Michael adducts. To evaluate the status of oxidative stress in the serum of type 2 diabetes mellitus, we constructed a sandwich enzyme-linked immunosorbent assay to measure serum HNE-modified albumin by the use of a specific monoclonal antibody (HNEJ-2) against HNE-histidine adducts as well as an antibody against human serum albumin. Serum of type 2 diabetes outpatients revealed significantly higher levels of HNE-modified albumin (736.1 +/- 34.2 pmol/ml, n = 54) than the matched nondiabetics (611.4 +/- 39.1 pmol/ml, n = 30; means +/- SEM; p = 0.018). However, no significant correlation was observed in diabetic outpatients between the levels of HNE-modified albumin and clinical parameters such as fasted blood glucose, HbA1c, diabetes duration, or complications. Our data demonstrated the increased formation of serum HNE-modified albumin in type 2 diabetic outpatients in the milieu between liver and vascular lumina, indicating the presence of oxidative stress.
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PMID:Serum 4-hydroxy-2-nonenal-modified albumin is elevated in patients with type 2 diabetes mellitus. 1121 73

Transplantation of encapsulated islets may restore endogenous insulin secretion in type 1 diabetics with no need of lifetime immunosuppression of the recipient. A biomaterial should be developed which combined immunoisolation with rapid and efficient diffusion of glucose and insulin. Rat islets were macroencapsulated in capillaries (molecular cut off 50 kD) of differently modified polysulphone. Macroencapsulated islets were perifused to study the kinetics of glucose induced insulin secretion into the perifusion medium. Blending polysulphone (PSU) with poly vinyl pyrrolidone or sodium dodecyl sulphate was not suited for islet macroencapsulation since glucose induced insulin release was absent after encapsulation. Hydroxy methylation (CH2OH) of PSU improved the secretory behaviour of macroencapsulated islets depending on the degree of substitution (DS). At 0.8 DS glucose induced insulin secretion was delayed and inefficient. At maximal degrees of PSU-substitution (1.8) the kinetics of insulin release and the efficiency of insulin release were very similar to that observed of free floating islets. In conclusion, highly substituted hydroxy methylated polysulphone allows a rapid and efficient insulin release after macroencapsulation and is suited for the further development of a bioartificial pancreas.
Exp Clin Endocrinol Diabetes 2001
PMID:Macroencapsulation of rat islets without alteration of insulin secretion kinetics. 1134 Dec 99


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