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 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

Sprague-Dawley rats were separated in 4 groups. G1 received streptozotocin (ST). G2 received nicotinamide (NC) followed by ST. G3 was a NC control and G4 was a citrate control. The rats were sacrificed after 28 h and the islets isolated. Histamine and histaminase were determined. In the islets there was an increase in histamine content in G1 and a smaller increase in G2. The first two groups differ significantly and also in relation to the control groups. A decrease in islet histaminase does not seem responsible for the increased histamine, since group 2 (NC + ST) which had no diabetes, had a lower activity than group 1 (ST). It is suggested that histamine liberation by ST may be related to the diabetogenic effect of this drug.
Diabetes Res Clin Pract
PMID:Early increase in histamine concentration in the islets of Langerhans isolated from rats made diabetic with streptozotocin. 170 Nov 17

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

Streptozotocin-induced diabetes in rats has been used to study the effect of insulin deficiency on histamine metabolism. There were significant increases in the amine content in the pancreas and intestine, and a significant drop in intestinal diamine oxidase (DAO) activity. The reduced DAO activity may be of clinical relevance.
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PMID:Histamine metabolism in diabetic rats. 211 41

In view of the observations that (1) plasma histamine concentrations are significantly higher in diabetic patients and diabetic rats than those in controls, and (2) tissue concentrations of histamine are elevated in rats with experimental diabetes, we have investigated histamine synthesis, as reflected by histidine decarboxylase (HDC) activity, and histamine catabolism, as reflected by histaminase activity, in various tissues of the diabetic rat. Rats with streptozotocin-induced diabetes mellitus (DM) showed an increase in histamine synthesis in various tissues; this was most marked in the aorta and to a lesser, but significant, extent in the kidneys, lungs, and heart, but not in the brain, stomach, or skin. Tissue content of histamine was significantly increased in all tissues except the stomach and skin. We conclude that tissue histamine synthesis is significantly increased in diabetic animals and that this increase is most marked in the aorta. The elevation in HDC activity in these tissues probably accounts for the increase in tissue and plasma concentrations of histamine in diabetic animals, since there is no change in histamine catabolism. This increase in histamine synthesis and release may contribute to the pathogenesis of endothelial damage in diabetic microangiopathy and macroangiopathy.
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PMID:Histamine synthesis and catabolism in various tissues in diabetic rats. 237 78

Serum monoamine oxidase, diamine oxidase and lysyl oxidase-like activity were measured in patients with granuloma annulare (GA), necrobiosis lipoidica (NL) and diabetes mellitus. In diabetes, all enzyme measurements were raised by a factor of about 2 X 2, and in NL by a factor of about 1 X 5. The rise in patients with GA was small and only significant in the case of benzylamine monoamine oxidase. "Stiff' collagen would seem to link these three disorders and the present results suggest that these amine oxidases could be useful in monitoring collagen abnormality in diabetes and diabetes-associated disorders, particularly in the absence of chronic liver disease. A negative correlation was found between enzyme activity and blood glucose levels, thus collagen changes in these conditions may occur independently of elevated blood glucose levels. Possible involvement of these enzymes in angiopathy remains to be elucidated.
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PMID:Increased activity of serum amine oxidases in granuloma annulare, necrobiosis lipoidica and diabetes. 288 24

We studied histamine metabolism, i.e., histidine decarboxylase (HD)-mediated synthesis and histaminase-mediated catabolism, in relation to intracellular histamine content in both aortic endothelial and subjacent smooth muscle cells of control and diabetic rats. Diabetes was induced by a single jugular vein injection of streptozotocin (55 mg/kg in acidified saline, pH 4.5), and animals were held for either 2 or 4 weeks following overt manifestation of diabetes. An additional 4-week diabetic group received insulin (Iletin NPH, 10 U per 24 hour) during the last week. With respect to control values, the histamine content of aortic endothelial cells increased 138%, HD activity increased 250%, and histaminase activity decreased 50% over the 4-week period. In subjacent smooth muscle cells, the histamine content increased in excess of 150%, HD activity increased more than 300%, and histaminase activity decreased in excess of 30%. Insulin treatment for the last week resulted in complete reversal of all these changes. These results support the concept that a large vessel response similar to the microcirculatory prolonged phase of inflammation occurs in experimental diabetes, a change similar to that occurring in experimental atherosclerosis. They also indicate that both synthetic and catabolic changes occur in histamine metabolism under these conditions, changes that alter arterial wall histamine pools, and suggest that insulin administration under conditions of experimental diabetes may modulate aortic histamine metabolism and the resultant intraaortic histamine pools.
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PMID:Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes. 680 15

1. Semicarbazide-sensitive amine oxidase is a common name for a group of heterogeneous amine oxidases which are present in various mammalian tissues, especially in vascular smooth muscle cells, cartilage and adipose tissue, but also in plasma. 2. Plasma semicarbazide-sensitive amine oxidase activity was elevated in a group of 104 patients with insulin-dependent diabetes mellitus compared with normal control subjects (555 +/- 172 versus 352 +/- 102 m-units/l, P < 0.0005). 3. Plasma semicarbazide-sensitive amine oxidase activity was higher in subgroups with either retinopathy or nephropathy or both [583 +/- 116 (n = 34), 581 +/- 229 (n = 10) and 646 +/- 249 m-units/l (n = 19), respectively] than in the subgroup without overt complications [486 +/- 129 m-units/l (n = 41), P < 0.005]. 4. Plasma semicarbazide-sensitive amine oxidase activity was positively correlated with plasma glycosylated haemoglobin (r = 0.40; P < 0.0001) and with log urinary albumin excretion (r = 0.26; P < 0.025). 5. The possibility that semicarbazide-sensitive amine oxidase, by its conversion of endogenous amines like methylamine and aminoacetone into cytotoxic aldehydes, plays a role in the development of microvascular complications in diabetes mellitus, needs further investigation.
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PMID:Plasma semicarbazide-sensitive amine oxidase activity is elevated in diabetes mellitus and correlates with glycosylated haemoglobin. 763 51

Methylamine was observed to be deaminated by several semicarbazide-sensitive amine oxidases, which were prepared from blood and vascular tissues of various species, including humans. Although methylamine itself is relatively nontoxic toward endothelial cells obtained from both human umbilical vein and calf pulmonary artery, it becomes very toxic in the presence of SSAO. SSAO inhibitors (i.e., MDL-72974A) effectively protected the cells from methylamine-SSAO-induced damage. The cytotoxicity seems, therefore, to be a consequence of the deamination of methylamine. Our findings suggest that formaldehyde, the deaminated product of methylamine, may be responsible for these toxic effects. Human serum, which also contains SSAO, was also capable of deaminating methylamine and causing cytotoxicity to cultured endothelial cells. Both methylamine and SSAO circulate in human blood, and their concentrations in the blood of normal healthy subjects are quite close to those required to induce cytotoxicity in tissue-cultured cells. Both SSAO activity and methylamine levels have been reported to be increased in the blood of diabetic individuals. Blood SSAO activity also has been reported to be elevated in the blood of STZ-induced diabetic rats. It is possible, therefore, that an abnormal metabolism of methylamine may be involved in endothelial injury, and that it may subsequently induce atherosclerotic plaque formation and thus be involved in the cardiovascular disorders seen in diabetes.
Diabetes 1993 Apr
PMID:Oxidative deamination of methylamine by semicarbazide-sensitive amine oxidase leads to cytotoxic damage in endothelial cells. Possible consequences for diabetes. 845 11

The widespread distribution of enzymes classed as semicarbazide-sensitive amine oxidases (SSAO enzymes) throughout a very wide range of eukaryotic as well as prokaryotic organisms encourages the aspirations of those who wish to demonstrate physiological, pathological or pharmacological importance. Such enzymes are found in several tissues of mammals, both freely soluble, as in blood plasma, and membrane-bound, for example, in smooth muscle and adipose tissue. While they are capable of deaminating many amines with the production of an aldehyde and hydrogen peroxide, doubt still surrounds the identity of the most important endogenous substrates for these enzymes. At present, methylamine and aminoacetone appear to head the list of candidates. The possibility that SSAO enzymes can convert amine substrates to highly toxic metabolites is illustrated by the production of acrolein from the xenobiotic amine, allylamine and formaldehyde and methylglyoxal from methylamine and aminoacetone, respectively. Activities of SSAO enzymes may be influenced by physiological changes, such as pregnancy or pathologically by disease states, including diabetes, tumours and burns. Increased deamination of aminoacetone by tissue and plasma SSAO enzymes as a result of its increased production from L-threonine in conditions such as exhaustion, starvation and diabetes mellitus may be harmful. Such dangers could be mitigated either physiologically by a compensatory reduction in SSAO activity or pharmacologically by treatment with inhibitors of SSAO.
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PMID:Some aspects of the pathophysiology of semicarbazide-sensitive amine oxidase enzymes. 858 67


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