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)

In an experimental model of insulin-dependent diabetes mellitus (IDDM) in the teleost fish, the goby Gillichthys mirabilis, an isletectomy procedure completely removes the pancreatic endocrine tissue without affecting the exocrine acini or other essential tissues. Interestingly, isletectomized (Ix) gobies do not exhibit a significant hyperglycemia until 10-15 d after this procedure, suggesting a lack of initial diabetogenic actions of a pancreatic factor(s). Administering exogenous glucagon in otherwise nonsymptomatic 7-d Ix gobies, however, induces a hyperglycemic state comparable to that in severely diabetic rats or gobies (after 20 d post-Ix). The spontaneously arising hyperglycemia observed between 10 and 15d post-Ix, on the other hand, is significantly correlated with increasing serum cortisol concentrations, with both exhibiting sustained elevated levels (approx 23 mmol/L and >100 ng/mL, respectively) at 20- and 25-d post-Ix. Exogenous cortisol treatment also significantly induced hyperglycemia in nonsymptomatic, 7-d Ix gobies. By contrast, growth hormone (GH) had no detectable diabetogenic effect in 7-d Ix gobies. Serum levels of ammonia, the principal nitrogenous waste in this species, were not affected by glucagon treatment but were reduced slightly by GH treatment (30% reduction; p < 0.05). Cortisol treatment, on the other hand, increased ammonia levels twofold, suggesting that the glucocorticoid induces a negative nitrogen balance. These results indicate that the counterregulatory hormones--glucagon and cortisol--are effective diabetogenic factors in the Ix goby, capable of driving metabolic imbalance in this model of IDDM.
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PMID:Diabetogenic role of insulin's counterregulatory hormones in the isletectomized, diabetic goby. 1121 38

Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of methylamine and aminoacetone to produce toxic aldehydes, i.e. formaldehyde and methylglyoxal, as well as hydrogen peroxide and ammonia. An increase of SSAO activity was detected by different laboratories in patients suffering from vascular disorders, i.e. diabetes and myocardial infarction. The enzyme has been suggested to play a role in vascular endothelial damage and atherogenesis. To date, there are no selective SSAO inhibitors. In the present study, 2-bromoethylamine (2-BrEA) was found to be a highly effective and selective inhibitor of SSAO obtained from different sources. The inhibition was irreversible and time dependent. It was competitive when the enzyme was not preincubated with the inhibitor, but became noncompetitive after incubation of the enzyme with 2-BrEA. The aldehyde trapping agent o-phenylenediamine was capable of preventing 2-BrEA-induced inhibition of SSAO activity. An aldehyde product was detected to be an initial product of 2-BrEA after it was incubated with SSAO. The inhibition, therefore, is mechanism-based. The SSAO inhibitory effects of eight structural analogues of 2-BrEA were assessed. It was concluded that a bromine atom at the beta position is quite important for exerting high potency of SSAO inhibition. The inhibition of SSAO activity by 2-BrEA was also demonstrated in vivo. It increased the urinary excretion of methylamine, an endogenous substrate for SSAO, in mice. 2-BrEA can be employed as a very useful tool in the investigation of SSAO.
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PMID:2-Bromoethylamine as a potent selective suicide inhibitor for semicarbazide-sensitive amine oxidase. 1126 60

Plasma activity of the enzyme semicarbazide-sensitive amine oxidase (SSAO) is high in diabetes. Production of angiotoxic substances (an aldehyde, hydrogen peroxide, and ammonia) in vessel walls is catalysed by SSAO, suggesting a role for SSAO in the development of complications of diabetes. The objective of the present study was to follow up plasma SSAO activity (measured radiometrically), HbA(1c) (using ion exchange chromatography), and retinopathy (by fundus photography) after 2.8 years, in 34 patients with Type 2 diabetes. We also measured urinary levels of an SSAO substrate, methylamine, by fluorometric high-performance liquid chromatography (HPLC). As at baseline, plasma SSAO activity was now higher in subjects with retinopathy (mean 19.5) than in subjects without retinopathy (mean 16.0), 95% confidence interval (CI) for difference 0.6-6.3 nmol benzylamine ml(-1) plasma h(-1). SSAO activity had not changed significantly since baseline, mean difference -1.65 and 95% CI for difference -3.76 to 0.46 nmol benzylamine ml(-1) plasma h(-1). Mean HbA(1c) level remained higher for patients with retinopathy (now 7.9%) compared to those without retinopathy (6.1%), 95% CI for difference 0.6-3.0%. Comparing baseline and the present study, retinopathy was nonproliferative; level had worsened for five and improved for two patients. Urinary methylamine/creatinine ratio was lower in the group of patients with retinopathy (mean 0.99) than in those without retinopathy (mean 1.78), 95% CI for difference 0.1-1.5 microg mg(-1). The results of the present study are compatible with a role for SSAO in the development of diabetic retinopathy.
J Diabetes Complications
PMID:Follow-up of plasma semicarbazide-sensitive amine oxidase activity and retinopathy in Type 2 diabetes mellitus. 1152 99

No intravenously injectable enzyme preparate containing urease as an alternetive to hemodialysis, hemoperfusion and CAPD systems in patients having chronic renal failure has been encountered in literature. In this study, it has been aimed to convert blood urea to alanine by using PEG-urease/PEG-AlaDH enzyme pair encapsulated within living erythrocyte. In this system, urea is decomposed into NH3 and HCO3- and the ammonia released is converted into alanine by reacting pyruvate under the catalytic action of alaninedehydrogenase. The production of pyruvate and NADH by erythrocyte required in the second stage of the reaction will make the process a feasible and ceaseless one. The success of the system will enable the renal patients with diabetes mellitus. Urease and AlaDH were covalently immobilized on activated PEG. PEG-urease/PEG-AlaDH were encapsulated in erythrocyte (1/1)(v/v) by using slow dialysis methods. The activity of enzyme system, encapsulation yield and hemogram analysis were determined for each sample.
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PMID:Encapsulation of PEG-urease/PEG-AlaDH enzyme system in erythrocyte. 1170 64

Cultured human umbilical vein endothelial cells (HUVEC) were used as a model to study transendothelial IGF-I transport, and its deposition into the extracellular matrix (ECM). Specific binding of (125)I-IGF-I to HUVEC monolayers was demonstrated, which was inhibited by aIR-3, a specific antibody directed against the IGF-I receptor. ECM-associated (125)I-IGF-I was approximately 10% of cell-bound IGF-I at 22 degrees C, and increased 4.5-fold at 37 degrees C, indicating that endothelial metabolism is required for the transport. However, neither monensin and cytochalasin B, both of which block endocytosis, nor aIR-3 did inhibit transport of (125)I-IGF-I into the ECM. In order to characterize IGF-I binding to the subendothelial ECM, HUVEC were removed nonenzymatically by treatment with Triton X-100 and ammonia. Specific, saturable binding of (125)I-IGF-I to the isolated ECM was observed, which was protease-sensitive. Antibodies directed against vitronectin inhibited IGF-I binding to the matrix by 35%, while antibodies directed against other ECM proteins had no significant influence on IGF-I binding. Using radioimmunoassays the IGF binding protein-2 was detected in the ECM, while IGFBP-1 and IGFBP-3 were below the detection limits. In order to evaluate functional aspects of IGF-I binding to the matrix, HUVEC were incubated under serum-free conditions in the absence and presence of IGF-I. Under serum-free conditions 48% of cells rounded up and started to detach after 2 hours incubation, while only 23% of the cells started to detach in the presence of IGF-I. These data indicate that IGF-I is transported via a paracellular route across endothelial cells, and becomes bound to the subendothelial ECM. Vitronection seems to be involved in binding of IGF-I to the ECM. ECM-associated IGF-I might play a role in endothelial cell survival and stability.
Exp Clin Endocrinol Diabetes 2002 Apr
PMID:Transport of insulin-like growth factor-I across endothelial cell monolayers and its binding to the subendothelial matrix. 1192 68

Expression of high activities of both glutamine synthetase and glutaminase allows the liver to play a major role in the regulation of glutamine homeostasis. The liver shows net glutamine output in metabolic acidosis, in prolonged starvation and animals bearing tumors, net glutamine uptake in the postabsorptive state, on consuming high protein diets, and in uncontrolled diabetes or sepsis. Liver glutamine synthetase is expressed only in a small population of perivenous cells that allows it to salvage any ammonia not incorporated into urea in periportal cells. Hepatic glutaminase is a unique isozyme found only in periportal liver parenchymal cells where it provides glutamate and ammonia for the urea cycle. Control of hepatic glutamine metabolism occurs almost exclusively through changes in the activity of glutaminase, with no change in glutamine synthetase flux.
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PMID:Hepatic glutamine metabolism. 1193 40

L-Glutamine: D-fructose-6-phosphate amidotransferase, known under trivial name of glucosamine-6-phosphate synthase, as the only member of the amidotransferase subfamily of enzymes, does not display any ammonia-dependent activity. This enzyme, catalysing the first committed step in a pathway leading to the eventual formation of uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), is an important point of metabolic control in biosynthesis of amino sugar-containing macromolecules. The molecular mechanism of reaction catalysed by GlcN-6-P synthase is complex and involves both amino transfer and sugar isomerisation. Substantial alterations to the enzyme structure and properties have been detected in different neoplastic tissues. GlcN-6-P synthase is inflicted in phenomenon of hexosamine-induced insulin resistance in diabetes. Finally, this enzyme has been proposed as a promising target in antifungal chemotherapy. Most of these issues, especially their molecular aspects, have been extensively studied in recent years. This article provides a comprehensive overview of the present knowledge on this multi-facets enzyme.
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PMID:Glucosamine-6-phosphate synthase--the multi-facets enzyme. 1204 98

Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1+/-17.5 vs 63.2+/-14.9 mg 100 g(-1) min(-1), P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28+/-0.35; controls, 1.55+/-0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81+/-17 ml 100 g(-1) min(-1); saline, 75+/-19 ml 100 g(-1) min(-1), P=NS) or MVR (deferoxamine, 1.0+/-0.5 mmHg ml(-1) 100 g(-1) min(-1); saline, 1.2+/-0.6 mmHg ml(-1) 100 g(-1) min(-1), P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary microvasculature to sympathetic stimulation. Hydroxyl radicals may play a role in the pathogenesis of flow abnormalities in type 1 diabetes.
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PMID:Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus. 1211 Nov 29

This study assessed whether painful diabetic neuropathy is associated with abnormal sympathetic nervous function in the affected limbs. Nine patients with diabetes (four men, five women; age 61 +/- 7 years) and painful peripheral neuropathy of the feet, but without evidence of generalized autonomic neuropathy, underwent intravenous infusion of tritiated norepinephrine (NE) and sampling of arterial and venous blood in both feet and in one arm to quantify the rate of entry of NE into the local venous plasma (NE spillover). In the same patients, positron emission tomography (PET) scanning after intravenous injection of the sympathoneural imaging agent 6-[(18)F]fluorodopamine was used to visualize sympathetic innervation and after intravenous [(13)N]ammonia to visualize local perfusion. The results were compared with those in the feet of normal volunteers and in an unaffected foot of patients with unilateral complex regional pain syndrome (CRPS). In addition, neurochemical results obtained in painful diabetic neuropathy were compared with those obtained in diabetic control patients with painless neuropathy and diabetic control patients without neuropathy. Local arteriovenous difference in plasma NE levels (DeltaNE(AV)) and NE spillover in the arms did not differ across the groups. However, DeltaNE(AV) in the feet was significantly less in the group with painful diabetic neuropathy than in the control groups. Also NE spillover in the feet tended to be lower in painful neuropathy. DeltaNE(AV) of diabetic control patients without neuropathy (n = 6) resembled values in the control groups without diabetes, whereas patients with painless diabetic neuropathy (n = 6) had evidence suggesting partial loss of sympathetic innervation. PET scanning revealed decreased flow-corrected 6-[(18)F]fluorodopamine-derived radioactivity in patients with painful diabetic neuropathy, compared with values in normal volunteers and patients with CRPS. The results provide neurochemical and neuroimaging evidence for regionally selective sympathetic denervation in the painful feet of patients with diabetic neuropathy.
Diabetes 2002 Dec
PMID:Local sympathetic denervation in painful diabetic neuropathy. 1245 12

Arginine, a semi-essential amino acid, is involved in numerous areas of human biochemistry, including ammonia detoxification, hormone secretion, and immune modulation. Arginine is also well known as a precursor to nitric oxide (NO), a key component of endothelial-derived relaxing factor, an endogenous messenger molecule involved in a variety of endothelium-dependent physiological effects in the cardiovascular system. Because of arginine's NO-stimulating effects, it can be utilized in therapeutic regimens for angina pectoris, congestive heart failure, hypertension, coronary heart disease, preeclampsia, intermittent claudication, and erectile dysfunction. In addition, arginine has been studied in the treatment of HIV/AIDS, athletic performance, burns and trauma, cancer, diabetes and syndrome X, gastrointestinal diseases, male and female infertility, interstitial cystitis, immunomodulation, and senile dementia. Toxicity, dosage considerations, and contraindications are also reviewed.
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PMID:Arginine: Clinical potential of a semi-essential amino acid.. 1249 75


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