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)

The two hydrazone-compounds 2-(phenylethylhydrazono)-propionic acid (PEHP) and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid (CHEHP) significantly lowered the blood glucose level in several laboratory animals fasted 48 hours (guinea pigs, mice, hamsters and rats). In the guinea pig, PEHP produced a three times stronger hypoglycemic effect than phenelzine, its corresponding hydrazine. Conversely both hydrazono compounds decreased the monoamine oxidase activity much less, than phenelzine. CHEHP (145 mumol/kg) inhibited this enzyme by less than 14%. After oral administration both hydrazones (200 mumol/kg) also produced a distinct hypoglycemic effect. The blood glucose lowering properties of the two hydrazones were most manifest in fasted guinea pigs, diabetic mice and rats with streptozotozin diabetes.
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PMID:Hydrazonopropionic acids, a class of hypoglycemic substances. 1. Hypoglycemic effect of 2-(phenylethylhydrazono)- and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid. 53 78

Insulin-dependent diabetics show a significant reduction in blood platelets' monoamine oxidase (MAO) activity when compared with age-matched and sex-matched controls. This does not appear to be the case for diabetics either on diet control or receiving oral hypoglycemic drugs. The important role of this enzyme in the regulation of the circulating levels of a number of monoamines known to have an inhibitory effect on insulin secretion may indicate the possible inclusion of the MAO/monoamine system in the pathophysiology of diabetes. The possibility of using platelets' MAO activity as a biologic marker for a subgroup of insulin-dependent diabetics is also discussed.
Diabetes 1979 May
PMID:Reduced monoamine oxidase activity in blood platelets from insulin-dependent diabetic subjects. 57 77

The purpose of the investigations was the determination of the maximum gastric secretion during hyperglycaemia in healthy subjects as well as in patients with short-term and long-term diabetes. After the stimulation with pentagastrine, given in the dose of 6 microgram per kg of body weight in 0.9% sodium chloride solution continuous intravenous infusion, there were determined MAO, parietal and nonparietal secretions, the concentrations of sodium, potassium, chloride, calcium and magnesium, and the total secretin of these electrolytes in gastric juice. In healthy subjects hyperglycaemia was induced by intravenous infusion of 30% glucose solution. Under the influence of hyperglycaemia the decrease of MAO (p less than 0.001) in healthy subjects as well as in diabetics was found. In healthy subjects the decrease of the total potassium, chloride and magnesium secretion in gastric juice (p less than 0.001) was observed. In patients with long-term diabetes the decrease of the secretion of sodium, potassium, chloride, magnesium and calcium was observed. There were no differences in gastric secretion in both groups of diabetics. The inhibitory effect of hyperglycaemia on the parasympathetic system and the decreased release of endogenous gastrine may be the causes of these changes. Insulin may also inhibit gastric secretion.
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PMID:[Maximal gastric secretion in hyperglycemia in normal subjects and in diabetics]. 59 33

Simple bedside measurements of blood pressure and systolic pressure response to the Valsalva maneuver will confirm a clinical impression of orthostatic hypotension. Careful questioning of the patient usually elicits other symptoms of autonomic nervous system dysfunction, such as impotence, urinary and fecal incontinence, constipation or diarrhea, blurred vision, or sweating changes. Drugs are the most common cause of autonomic dysfunction, and their benefits should be weighed against the severity of the dysfunction. In addition, diabetes mellitus, uremia, amyloidosis, acute intermittent porphyria, myeloma, tabes dorsalis, and alcohol-nutritional problems may produce symptoms of autonomic dysfunction. Thus, patients who present with autonomic features but no history of dysfunction-producing drugs should undergo complete laboratory evaluation. A regimen of tyramine or L-dopa or a diet rich in cheese, processed meats, and wine (a monoamine), coupled with a monoamine oxidase inhibitor have beneficial effects in patients with orthostatic hypotension due to preganglionic autonomic dysfunction. Patients who do not respond to catecholamine precursors have stable, isolated orthostatic hypotension or a polyneuropathy such as that caused by diabetes.
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PMID:Evaluating dysfunction of the autonomic nervous system. 63 67

I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks old) with severe diabetic-like symptoms (blood glucose is greater than 300 mg./100ml.). In the spleen, vas deferens, and adrenal glands of the same animals the NE levels were not changed in relation to control. Other measurements of NE in young (six weeks old) diabetic mice revealed no differences between diabetic and nondiabetic controls. The turnover of NE, a measure of the functional state of sympathetic nerves, decreased significantly in the heart and salivary glands of 24-week-old mice but remained unchanged in the kidney and spleen. In young, diabetic mice the rates of NE turnover in several organs were similar to those found in age-matched controls. The hearts of 24-week-old diabetic mice contained significantly less dopamine-beta-hydroxylase (DBH), an intraneuronal enzyme active in the terminal step of NE biosynthesis. The kidney of the same animals was hypertrophic and showed a massive elevation of monoamine oxidase (MAO), an enzyme that degrades NE to inactive products. Other experiments showed that the regeneration of sympathetic neurons that follows the reversible chemical denervation with 6-hydroxydopamine was comparable in diabetic and nondiabetic animals. It appears that mice with spontaneous diabetes show changes of sympathetic nerve function similar to those noted in diabetic patients with autonomic neuropathy.
Diabetes 1978 Oct
PMID:The functional state of sympathetic nerves in spontaneously diabetic mice. 70 Feb 60

The treatment of obesity is one of the major measures available today in the field of preventive medicine. In particular, the coronary epidemic of Western civilisation would be halted, and most cases of maturity-onset diabetes prevented, if obesity were to be treated effectively. Anorectic drugs act mainly on the satiety centre in the hypothalamus to produce anorexia. They also have various metabolic effects involving fat and carbohydrate metabolism, but many of these may be secondary to loss of weight. Most of the drugs are related directly or indirectly to amphetamine and in addition act by increasing general physical activity. Anorectic drugs tend to lose their effect after some months, and part of this reduction in effect may be due to chemical alterations produced by the drugs in the brain. All the drugs, with the exception of fenfluramine, have a stimulant effect on the central nervous system in some individuals, resulting in restlessness and nervousness, irritability and insomnia. Fenfluramine commonly produces drowsiness in normal doses, but has stimulant effects with overdosage. Dexamphetamine, phenmetrazine and benzphetamine all tend to cause euphoria and the risk of addiction is therefore considerable. Euphoria occasionally occurs with diethylpropion, phentermine and chlorphentermine, but to a much lesser extent. Side-effects also occur due to sympathetic stimulation and gastro-intestinal irritation. These side-effects may cause some individuals to stop taking the drug, but are never serious or dangerous. Drug interactions may occur with monoamine oxidase inhibitors and to a clinically unimportant extent, with antihypertensive drugs. The anorectic drugs have a very definite part to play in the treatment of obesity, mainly for those individuals who have altered their eating habits but have come to a plateau of weight which they find difficult to get below. The drugs are best given in a long-acting form and can safely be continued as long as weight loss persists, provided that the clinician exercises careful supervision. Dexamphetamine, phenmetrazine and benzphetamine should rarely be used because of the danger of addiction, and chlorphentermine is potentially hazardous for long-term use. Diethylpropion emerges as the drug of first choice, as fenfluramine has a tendency to cause depression and has a higher incidence of side-effects. Fenfluramine is mainly useful for people who are especially tense and for obese maturity-onset diabetics who have been unable to lose weight with the biguanides. Mazindol and phentermine appear to be useful as alternative drugs.
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PMID:Anorectic drugs: use in general practice. 78 35

The capacity of the vascular enzyme, semicarbazide-sensitive amine oxidase (SSAO), to metabolize methylamine to the potentially toxic product, formaldehyde, was tested using rat aortic homogenates and purified porcine aortic SSAO. Formaldehyde production in incubations of enzyme source with methylamine (1 mM) was detected by high performance liquid chromatography and product was confirmed by desorption chemical ionization mass spectrometry (DCI-MS). Inhibitor studies using the specific SSAO inhibitor semicarbazide and the monoamine oxidase inhibitor pargyline indicate that SSAO is responsible for metabolism of methylamine to formaldehyde. These results suggest the possibility that elevated methylamine found in several pathologic states (such as uremia and diabetes mellitus), or generated from exogenous sources, could result in overproduction of formaldehyde in tissues with high SSAO activity, especially blood vessels.
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PMID:Methylamine metabolism to formaldehyde by vascular semicarbazide-sensitive amine oxidase. 163 2

A copper-containing amine oxidase is present in sheep blood plasma and has a high capacity to deaminate spermine and spermidine. The physiological function of this enzyme remains to be determined. Sheep blood plasma amine oxidase (SPAO) was measured by its ability to deaminate spermidine (700 microM) using a peroxidase-linked colorimetric assay developed for microtitre plates. SPAO activity has been studied in a group of Welsh Mountain sheep with experimental alloxan-induced diabetes. This resulted in an increase in SPAO activity which reached a peak of 70 days after alloxan treatment (60 per cent increase). This change could be seen in both pregnant and non-pregnant diabetic sheep. In normal pregnant ewes, SPAO activity remained stable for the first 100 days of pregnancy but declined by 50 per cent in the last month of pregnancy. Together, these findings suggest that SPAO activity is controlled by hormonal influences. This sensitive and convenient assay method could provide clues as to the physiological significance of SPAO and may be a useful clinical chemical indicator in the sheep.
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PMID:Physiological and pathological influences on sheep blood plasma amine oxidase: effect of pregnancy and experimental alloxan-induced diabetes mellitus. 188 42

NDMA, one of the most widely occurring carcinogenic compounds in the environment, is present in human food (meat, vegetables, cheese and alcohol beverages), in drinking water, in drugs, in cosmetics, in tobacco and its smokes. Furthermore NDMA may be synthesized from nitrates and nitrites and endogen or exogen amines. Since the first observations of MAGEE and BARNES in 1956 on the carcinogenicity of NDMA, this compound was reported to be carcinogenic in a large number of animal species including mammals, birds, amphibia and fish. NDMA requires metabolic activation for its cytotoxic and carcinogenic actions. The major activation step is believed to be the oxygenation of the alpha-carbon catalysed by a Cytochrome P-450-dependent enzyme system commonly know as NDMA-demethylase. Studies on the enzymology of NDMA metabolism show that some Cytochrome P-450 isozymes exhibit significant NDMA-demethylase activity only at high NDMA concentrations. The form of P-450 inducible by factors such as, fasting, diabetes, ethanol consumption and pretreatment with acetone, pyrazole or isopropanol has the higher affinity for NDMA. The gene coding for this isozyme belongs tho the P-450 II E subfamily. Because NDMA-demethylase activity is decreased by monoamine oxidase inhibitors, some authors have suggested a possible role of MAO in NDMA demethylation. This view is not supported by others who don't find evidence for an involvement of MAO in NDMA metabolism. Likewise, there are contradictory reports about the existence of some NDMA demethylase activity in cytosol, nuclei and mitochondria. NDMA demethylation, followed by nonenzymatic cleavage of the hydroxylated methyl group gives formaldehyde and methyldiazohydroxide and then leads to the formation of, a methonium ion, which is able to methylate nucleophilic sites of cellular macromolecules such as, proteins, RNA and DNA. A lot of studies suggest the existence of an alternative pathway to the formation of a methylating agent, denitrosation. Although the nature of mechanisms of denitrosation is not completely known, authors think that the formation of nitrite may represent a detoxification pathway rather than an activation pathway.
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PMID:[Biotransformation of dimethylnitrosamine]. 207 89

Metabolism of polyamines (spermidine and spermine) is known to be strictly related to the growth processes of eukaryotic cells. Since cell replication processes appear altered in insulin-dependent diabetes mellitus (IDDM), especially when associated with its microvascular complications, the aim of this study was measuring serum spermidine oxidase activity (SOA), a key enzyme in the metabolic pathway of polyamines, in 47 patients with IDDM as compared with 63 healthy control subjects matched for age and sex. Mean SOA levels +/- SD were significantly lower in IDDM patients (177.4 +/- 57.2 mu kat/l) than in controls (247.6 +/- 68.1 mu kat/l; p less than 0.001), being SOA inversely related with daily insulin dose. SOA was moreover significantly higher (but similar to controls) in the group with increased urinary albumin excretion rate (AER persistently greater than 20 micrograms/min); (n = 17; 213.1 +/- 62.6 mu kat/l) in comparison with normoalbuminuric subjects (n = 30; 156.6 +/- 43.5 mu kat/l; F = 21.78; p = 0.0001). SOA was correlated with AER (r = 0.45; p = 0.001), independently of age, duration of disease, serum creatinine, body weight, blood pressure and metabolic control, as shown by a multiple regression analysis model (p = 0.003). Presence of background retinopathy was not associated with modified levels of SOA, which was conversely higher, although not significantly, in the patients with proliferative retinal lesions. In conclusion serum SOA is deeply altered in IDDM patients, being markedly reduced in the whole group of patients and conversely independently increased up to the mean values of controls in presence of increased AER or advanced retinopathy.
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PMID:Serum spermidine oxidase activity in patients with insulin-dependent diabetes mellitus and microvascular complications. 208 31


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