Decrease In Catechol‐<i>O</i>‐Methyltransferase Activity In The Liver Of Streptozotocin‐Induced Diabetic Rats

Wang, J. P.; Liu, I-Min; Tzeng, Thing-Fong; Cheng, Juei‐Tang

doi:10.1046/j.1440-1681.2002.03673.x

Cited by 15 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activation of the adrenoceptor β1, as demonstrated in this study, is combined with the well-known increase of noradrenaline content [38] and catecholamine metabolism [45]. This effect is likely to be due to a decrease in catechol-O-methyltransferase activity in a rat model of type 1 diabetes when stressed [48]. We were able to confirm these results in our rat model of type 1 diabetes.…”

Section: Discussionsupporting

confidence: 86%

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

et al. 2011

View full text Add to dashboard Cite

Aims/hypothesis It is well documented that melatonin influences insulin secretion mediated by G-protein-coupled melatonin receptor isoforms MT1 and MT2, which are present in rat and human pancreatic islets, as well as in rat insulinoma cells. Recent investigations have proven that hyperinsulinaemic Goto-Kakizaki (GK) rats, which are a rat model of type 2 diabetic rats, and humans have decreased melatonin plasma levels, whereas a streptozotocin-induced rat model of diabetes developed reduced insulin levels combined with increased melatonin levels. Methods Plasma levels of glucose, insulin and melatonin as well as RNA expression of pineal Aanat, Hiomt (also known as Asmt), insulin receptor, adrenoceptor β1 and the clock genes Per1 and Bmal1 (also known as Arntl) were determined in male and female LEW.1AR1-iddm rats as well as in insulin-substituted LEW.1AR1-iddm rats.Results Severe hypoinsulinaemia in diabetic LEW.1AR1-iddm rats was associated with decreased body weight and increased melatonin plasma levels combined with mainly elevated expression of Aanat, Hiomt, pineal insulin receptor and adrenoceptor β1. The changes were normalised by insulin substitution. Diurnal profiles of plasma melatonin and of antagonistic clock genes Per1 and Bmal1 were maintained in diabetic and insulin-substituted rats. Conclusions/interpretation The assumed causal relation between elevated melatonin and reduced insulin levels in LEW.1AR1-iddm rats is supported by the observation that insulin substitution normalised these changes. Further support for this interpretation comes from the observation that in GK rats an increase of plasma insulin was combined with a decrease of plasma noradrenaline (norepinephrine), the most important activator of melatonin synthesis. These relationships between the noradrenergic and insulin pathway support the existence of melatonin-insulin antagonism.

show abstract

Section: Discussionsupporting

confidence: 86%

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Hepatic and kidney functions, as well as the enzymes involved in phase I and phase II metabolism, underwent apparent changes in animals under diabetic status (Nadai et al, 1990;Sato et al, 1991;Watkins and Sherman, 1992;Runge-Morris and Vento, 1995;Raza et al, 1996;Engels et al, 1999;Tuñon et al, 1991;Wang et al, 2002;Borbás et al, 2006;Sindhu et al, 2006). Thus, it is not surprising that the metabolic behavior of mangiferin after its oral administration was subjected to great changes in rats under diabetic status compared with that in conventional rats.…”

Section: Discussionmentioning

confidence: 99%

“…The expression levels of several hepatic and intestinal cytochrome P450 (P450) isozymes, such as CYP1A1, -1A2, -1B1, -2B1, -3A1, -3A2, -3A4, -4A1, -4A2, and -2E1 (Raza et al, 1996;Engels et al, 1999;Borbás et al, 2006;Sindhu et al, 2006), as well as sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and catechol-O-methyltransferase (COMT) (Runge-Morris and Vento, 1995;Tuñon et al, 1991;Wang et al, 2002) involved in phase II metabolism are altered in STZ-induced diabetic rats. Furthermore, an increase in the hepatic blood flow rate (Sato et al, 1991), a higher incidence of hepatic impairment (Watkins and Sherman, 1992), and kidney function impairment (Nadai et al, 1990) were also reported in diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats

Liu

Pan

et al. 2012

Drug Metabolism and Disposition

View full text Add to dashboard Cite

ABSTRACT:To clarify the role of the intestinal flora in the absorption and metabolism of mangiferin and to elucidate its metabolic fate and pharmacokinetic profile in diabetic rats, a systematic and comparative investigation of the metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin (STZ)-induced diabetic rats was conducted. Forty-eight metabolites of mangiferin were detected and identified in the urine, plasma, and feces after oral administration (400 mg/kg). Mangiferin underwent extensive metabolism in conventional rats and diabetic rats, but the diabetic rats exhibited a greater number of metabolites compared with that of conventional rats. When the intestinal flora were inhibited, deglycosylation of mangiferin and sequential biotransformations would not occur. Pharmacokinetic studies indicated a 2.79-and 2.35-fold increase in the plasma maximum concentration and the area under the concentration-time curve from 0 to 24 h of mangiferin in diabetic rats compared with those for conventional rats, whereas no significant differences were observed between conventional rats and pseudo-germ-free rats. Further real-time quantitative reverse transcription-polymerase chain reaction results indicated that the multidrug resistance (mdr) 1a level in the ileum increased, whereas its level in the duodenum and the mdr1b mRNA levels in the duodenum, jejunum, and ileum decreased in diabetic rats compared with those in conventional rats. With regard to the pseudo-germ-free rats, up-regulated mdr1a mRNA levels and down-regulated mdr1b mRNA levels in the small intestines were observed. The diabetic status induced increased UDP-glucuronosyltransferase (UGT) 1A3, UGT1A8, UGT2B8, and sulfotransferase (SULT) 1A1 mRNA levels and decreased catechol-Omethyltransferase (COMT), UGT2B6, UGT2B12, and SULT1C1 mRNA levels. These results might partially explain the different pharmacokinetic and metabolic disposition of mangiferin among conventional and model rats.

show abstract

“…Besides, experimentally induced hyperglycemia has been reported to produce a significant increase in the catecholamine levels in different areas of the brain (Ramakrishnan et al, 2003). In addition, hypoinsulinemia and hyperglycemia have been shown to alter COMT, BDH and TH activities, which could explain the monoaminergic dysregulation observed (Gupta et al, 1992;Muñoz et al, 1984;Wang et al, 2002). Thus, amitraz's a 2 -adrenergic receptors action could contribute either directly or indirectly, through insulin dysregulation, to the observed effects on monoaminergic neurotransmitters.…”

Section: Discussionmentioning

confidence: 99%

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

et al. 2017

View full text Add to dashboard Cite

(2017). Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats. Chemosphere, 181 518-529. Amitraz is a formamidine insecticide/acaricide that alters different neurotransmitters levels, among other neurotoxic effects. Oral amitraz exposure (20, 50 and 80 mg/kg bw, 5 days) has been reported to increase serotonin (5-HT), norepinephrine (NE) and dopamine (DA) content and to decrease their metabolites and turnover rates in the male rat brain, particularly in the striatum, prefrontal cortex, and hippocampus. However, the mechanisms by which these alterations are produced are not completely understood. One possibility is that amitraz monoamine oxidase (MAO) inhibition could mediate these effects. Alternatively, it alters serum concentrations of sex steroids that regulate the enzymes responsible for these neurotransmitters synthesis and metabolism. Thus, alterations in sex steroids in the brain could also mediate the observed effects. To test these hypothesis regarding possible mechanisms, we treated male rats with 20, 50 and 80 mg/kg bw for 5 days and then isolated tissue from striatum, prefrontal cortex, and hippocampus. We then measured tissue levels of expression and/or activity of MAO, catechol-O-metyltransferase (COMT), dopamine-b-hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TRH) as well as estradiol levels in these regions. Our results show that amitraz did notAbbreviations: AD, aldehyde dehydrogenase; AMZ, amitraz; ARO, aromatase; AAADC, aromatic amino acid decarboxylase; CNS, central nervous system; COMT, catechol-O-metyltransferase; Ct, cycle threshold; DA, dopamine; DBH, dopamine-bhydroxylase; DOPA, 3,4-dihydroxyphenylalanine; DOPAC, 3,4-hydroxyphenylacetic acid; DHT, dihydrotestosterone; E2, 17b-estradiol; FC, prefrontal cortex; HC, hippocampus; HPLC, high performance liquid chromatography; HVA, homovanillic acid; 5-HT, serotonin; 5-HTP, 5-hydroxytryptophan; 5-HIAA, 5-hydroxy-3-indolacetic acid; LD 50 , Lethal Dose 50; LOQ, Quantification limit; MAO, monoamine oxidase; MHPG, 3-metoxy-4-hydroxyphenylethyleneglycol; NE, norepinephrine; NSD-1015, m-hydroxymethylhydrazine; SD, standard deviation; ST, striatum; T, testosterone; TH, tyrosine hydroxylase; TMX, tamoxifen; TRH, tryptophan hydroxylase.* Chemosphere 181 (2017) 518e529 inhibit MAO activity at these doses, but altered MAO, COMT, DBH, TH and TRH gene expression, as well as TH and TRH activity and estradiol levels. The alteration of these enzymes was partially mediated by dysregulation of estradiol levels. Our present results provide new understanding of the mechanisms contributing to the harmful effects of amitraz.

show abstract

Decrease In Catechol‐O‐Methyltransferase Activity In The Liver Of Streptozotocin‐Induced Diabetic Rats

Cited by 15 publications

References 14 publications

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

Contact Info

Product

Resources

About