Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arginase activity has been identified in the prostate, and may be important in the synthesis of polyamines in accessory sex glands in the male. Polyamines in turn may mediate the action of androgens. Diabetic patients have disordered androgen synthesis. The purpose of this work was to evaluate the effect of L-arginine on arginase activity in accessory sex glands of male rats under normal and diabetic conditions (alloxan 120 mg/kg, i.p.). Normal and diabetic male rats were untreated or were treated with insulin or L-arginine for 96 h, and sacrificed. Arginase activity was measured in serum and in accessory sex glands. Arginase activity in accessory glands did not change significantly with induction of diabetes. Arginase activity was increased in diabetic insulin-treated rats, but there was no arginase response to L-arginine administration in diabetic animals. These findings stand in contrast to beneficial effects of L-arginine previously observed when this amino acid was administered for a long time (at least 10 days). We suspect that altered arginase activity in accessory sex glands may play a role in the reproductive dysfunction caused by diabetes, inasmuch as arginase activity can be increased in experimentally diabetic rats by the administration of insulin.
 ...
PMID:Effect of L-arginine on arginase activity in male accessory sex glands of alloxan-treated rats. 1240 10

The effect of oral administration of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP), a medicinal plant used extensively in Asia, on the mitochondrial metabolism in the alloxan diabetic rats has been investigated. Rats were injected with alloxan monohydrate (20 mg/100 g body wt) or vehicle (Na-acetate buffer), the former were treated with either 2 IU insulin i.p., 0.6 mg/ml SOV ad libitum, 5% TSP ad libitum, and a combination of 0.2% SOV and 5% TSP ad libitum for 21 days. Selected rate-limiting enzymes of the tricarboxylic acid cycle, hydrogen shuttle system, ketone body metabolism, amino acid metabolism and urea cycle were measured in the mitochondrial and cytosolic fractions of liver, kidney and brain tissues of the experimental rats. Majority of the mitochondrial enzymes in the tissues of the diabetic rats had significantly higher activities compared to the control rats. Similarly, the activities of mitochondrial and cytosolic aminotransferases and arginase were significantly higher in liver and kidney tissues of the diabetic rats. The separate administrations of SOV and TSP to diabetic rats were able to restore the activities of these enzymes to control values. The lower dose of SOV (0.2%) administered in combination with TSP to diabetic rats lowered the enzyme activities more significantly than when given in a higher dose (0.6%) separately. This is the first report of the effective combined action of oral SOV and TSP in ameliorating the altered mitochondrial enzyme activities during experimental type-1 diabetes. Our novel combined oral administration of SOV and TSP to diabetic rats thus conclusively proves as a possible method to minimize potential vanadate toxicity without compromising its positive effects in the therapy of experimental type-1 diabetes.
 ...
PMID:Oral administration of orthovanadate and Trigonella foenum graecum seed power restore the activities of mitochondrial enzymes in tissues of alloxan-induced diabetic rats. 1284 30

Within the past years, an important role for nitric oxide (NO) in skin repair has been well defined. As NO is synthesized from L-arginine by NO synthases (NOS), the availability of L-arginine might be one rate-limiting factor of NO production at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity were strongly induced reaching a maximum between day 3 and day 7 postwounding. Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at epithelial sites at the margins of the wound. Notably, diabetes-impaired skin repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese, ob/ob) was characterized by an abnormally elevated arginase activity in wound tissue in the absence of an expression of iNOS. Expression analyses demonstrated that arginase-1 contributed to increased arginase activities in impaired repair. Interestingly, an improved healing of chronic wound situations in leptin-supplemented ob/ob mice was strongly associated with an adjustment of the dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS expression was upregulated early in repair and an augmented arginase-1 expression and activity was downregulated in the presence of markedly elevated numbers of macrophages during late repair. These data suggest a coordinated consumption of L-arginine by the NOS and arginase enzymatic pathways at the wound site as a prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis that drives a normal skin repair.
 ...
PMID:Expression and activity of arginase isoenzymes during normal and diabetes-impaired skin repair. 1467 8

Arginine, a semi-essential amino acid, plays a major nutritional and metabolic role. In particular, arginine is the precursor of nitric oxide which is involved in the endothelial function. Several factors, such as hypercholesterolemia, diabetes, ageing and hypertension are established risk factors for atherosclerosis, in particular by decreasing the availability of nitric oxide. Thus, endothelial nitric oxide synthase has a pivotal role against atherosclerosis. A suitable amount of cofactor and a sufficient intake of arginine have been shown to modulate nitric oxide-induced vasodilatation: despite the fact that the intracellular concentration of arginine is well above the Km of endothelial nitric oxide synthase, an arginine supplemented-diet is effective in increasing the production of nitric oxide. Several mechanisms have been proposed to explain this "arginine paradox": co-localization of the arginine transporter with endothelial nitric oxide synthase, intracellular arginine regeneration from citrulline, balance between endothelial arginase and nitric oxide synthase. Statins which are HMG-CoA reductase inhibitors inhibit the synthesis of mevalonate, and thus that of cholesterol. In addition, statins increase the stabilization of endothelial nitric oxide synthase mRNA. The co-operation between cholesterol synthesis and the upregulation of caveolin-1 on the one hand, and the activation of endothelial nitric oxide synthase on the other hand, is very tight. A depletion of cholesterol in the caveolae induces a decrease in caveolin-1 at the cell surface allowing NOS activation. Thus statins improve nitric oxide production and vasodilatation. In a recent work in the hypercholesterolemic Watanabe rabbit, we have demonstrated that the combination of arginine with a statin, namely atorvastatin, significantly hinders the spreading of atherosclerotic plaques as compared with monotherapies. Such association of a nutriment and a drug open a new area of therapeutic strategy.
 ...
PMID:[Arginine and statins: relationship between the nitric oxide pathway and the atherosclerosis development]. 1623 Feb 78

This study was conducted to evaluate possible alteration in the activity of arginase, an important enzyme of cell proliferation and vascular smooth muscle contraction regulator in diabetics, that may be correlated with low fertility in diabetic patients. In this investigation, 6 apparently healthy adult male dogs were selected and divided in two groups, diabetics and non-diabetics. Diabetes mellitus was induced in one group by intravenous (IV) injection of alloxan (100 mg/kg). Dogs with a fasting blood glucose (FBS) of more than 200 mg/dl were considered to be diabetic. Four weeks following induction of diabetes mellitus, the animals in both groups were anesthetized by an IV injection of sodium thiopental. Livers and whole reproductive systems, including the testes, penis, urethra, and prostate, were dissected. The epididymides, corpus cavernosum, corpus spongiosum, penile urethra, and vas deferens were also dissected and removed from the reproductive system. Arginase activity and total protein were measured by the urea and Lowry's methods respectively in above mentioned sections. Plasma testosterone was determined by the radioimmunoassay method. The results showed significantly (P<0.05) increased arginase specific activity (ASA) in the liver, epididymis, prostate, corpus cavernosum and corpus spongiosum of the diabetic dogs. In the reproductive system of the diabetic dog, the maximum and minimum ASA was seen in the corpus cavernosum and testes, respectively (105.12 +/- 8.76 vs. 25.0 +/- 0.55). No such variation was observed in the ASA of normal dogs (39.0 +/- 5.47 vs. 25.0 +/- 5.47). There was no significant difference in plasma testosterone level between the groups. In conclusion, diabetes increased the ASA in liver, prostate, epididymis, corpora cavernosa, and corpora spongiosum of the male dogs and may contribute to erectile dysfunction or low fertility in diabetics.
 ...
PMID:Arginase alteration in the reproductive system of alloxan-diabetic dogs. 1717 54

1. Arginase is the focal enzyme of the urea cycle hydrolysing L-arginine to urea and L-ornithine. Emerging studies have identified arginase in the vasculature and have implicated this enzyme in the regulation of nitric oxide (NO) synthesis and the development of vascular disease. 2. Arginase inhibits the production of NO via several potential mechanisms, including competition with NO synthase (NOS) for the substrate L-arginine, uncoupling of NOS resulting in the generation of the NO scavenger, superoxide and peroxynitrite, repression of the translation and stability of inducible NOS protein, inhibition of inducible NOS activity via the generation of urea and by sensitization of NOS to its endogenous inhibitor asymmetric dimethyl-L-arginine. 3. Upregulation of arginase inhibits endothelial NOS-mediated NO synthesis and may contribute to endothelial dysfunction in hypertension, ageing, ischaemia-reperfusion and diabetes. 4. Arginase also redirects the metabolism of L-arginine to L-ornithine and the formation of polyamines and L-proline, which are essential for smooth muscle cell growth and collagen synthesis. Therefore, the induction of arginase may also promote aberrant vessel wall remodelling and neointima formation. 5. Arginase represents a promising novel therapeutic target that may reverse endothelial and smooth muscle cell dysfunction and prevent vascular disease.
 ...
PMID:Arginase: a critical regulator of nitric oxide synthesis and vascular function. 1764 39

Increases in arginase activity have been reported in a variety of disease conditions characterized by vascular dysfunction. Arginase competes with NO synthase for their common substrate arginine, suggesting a cause and effect relationship. We tested this concept by experiments with streptozotocin diabetic rats and high glucose (HG)-treated bovine coronary endothelial cells (BCECs). Our studies showed that diabetes-induced impairment of vasorelaxation to acetylcholine was correlated with increases in reactive oxygen species and arginase activity and arginase I expression in aorta and liver. Treatment of diabetic rats with simvastatin (5 mg/kg per day, subcutaneously) or L-citrulline (50 mg/kg per day, orally) blunted these effects. Acute treatment of diabetic coronary arteries with arginase inhibitors also reversed the impaired vasodilation to acetylcholine. Treatment of BCECs with HG (25 mmol/L, 24 hours) also increased arginase activity. This effect was blocked by treatment with simvastatin (0.1 micromol/L), the Rho kinase inhibitor Y-27632 (10 micromol/L), or L-citrulline (1 mmol/L). Superoxide and active RhoA levels also were elevated in HG-treated BCECs. Furthermore, HG significantly diminished NO production in BCECs. Transfection of BCECs with arginase I small interfering RNA prevented the rise in arginase activity in HG-treated cells and normalized NO production, suggesting a role for arginase I in reduced NO production with HG. These results indicate that increased arginase activity in diabetes contributes to vascular endothelial dysfunction by decreasing L-arginine availability to NO synthase.
 ...
PMID:Diabetes-induced coronary vascular dysfunction involves increased arginase activity. 1817 71

Evidence indicates that nitric oxide (NO) deficiency contributes to micturition disorders, especially in the afferent pathway and erectile dysfunction (ED). Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine: ADMA) in plasma and tissues. Elevated tissues of ADMA and N(G)-monomethyl-L-arginine (L-NMMA) have been reported to be associated with impaired NO-mediated urethral, trigonal and cavernosal relaxations by pelvic ischemia. Also, plasma ADMA may help to identify underlying cardiovascular disease in men with ED. Decreased l-arginine availability to NO synthase is due to the shunting of L-arginine into other pathways such as arginase. Interaction between NO synthase and arginase has been reported to be involved in NO-mediated urethral and prostatic relaxations. Also, increased arginase activity in cavernosal tissues likely contributes to the ED that accompanies diabetes mellitus and aging. Therefore, arginase inhibition has been reported to enhance the NO-dependent physiological process for erectile function.
 ...
PMID:Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction. 1826 46

The aim of the presented experiments was to study the influence of suturated NAE--N-stearoylethanolamine (NSE) on the NO synthesis by NO-synthases in aorta and heart tissues of rats with developmental (12-week) streptozotocin-induced (50 mg/kg of body weight) diabetes. Also we evaluated the state of endothelium-dependent relax reactions of aorta smooth muscles. It was shown that the development of diabetes is accompanied with disbalance of NO-synthesis wich consist in inducible NOS (iNOS) activation and inhibition of constitutive NOS (cNOS) and arginase activities. The aorta smooth muscle endothelium-dependent relax reactions were decreased in diabetic rats. The NSE administration to rats with development streptozotocin-induced diabetes resulted in inhibition of iNOS activity and elevation of cNOS and arginase activities in these tissues. Normalization of NO-synthesis under NSE action was accompanied with restoration of aorta smooth muscle endothelium-dependent relax reactions in diabetic rats.
 ...
PMID:[The effects of n-stearoylethanolamine on the NO-synthase pathway of NO generation in the aorta and heart of streptozotocin-induced diabetic rats]. 1835 89

In experimental streptozotocin-induced diabetes, the activity of enzymes which have common substrate (L-arginine) changes in leucocytes of peripheral blood. It leads to misbalance between different pathways of arginine metabolism: NO-synthase (oxidative) pathway is activated, whereas arginase (nonoxidative) one is depressed. The injection of L-arginine under diabetes activated nonoxidative pathway, which can be seen in possible decrease in NO-synthase activity with unchanged arginase activity. After injection ofaminoguanidine in animals under diabetes the efficiency of both pathways in leucocytes decreases, which may be the basis of reconstitution of physiological pool to the relatively essential amino acid L-arginine.
 ...
PMID:[Peculiarities of L-arginine metabolism in the blood leukocytes in experimental diabetes mellitus]. 1841 86


<< Previous 1 2 3 4 5 6 7 8 9 Next >>