RESUMO
Baicalin is a plant-derived, biologically active compound exerting numerous advantageous effects. Adipocytes store and release energy in the process of lipogenesis and lipolysis. Rodent studies have shown that baicalin treatment positively affects fat tissue, however, data on the direct influence of this compound on adipocyte metabolism is lacking. In the present research, the short-term effects of 25, 50, and 100 µM baicalin on glucose transport, conversion to lipids, and oxidation, and also on lipolysis in primary rat adipocytes were explored. Lipolysis was measured as glycerol release from adipocytes. It was shown that 100 µM baicalin reduced glucose oxidation but at any concentration did not affect glucose transport and lipogenesis. Baicalin significantly increased the adipocyte response to physiological and pharmacological lipolytic stimuli (such as epinephrine - adrenergic agonist, DPCPX - adenosine A1 receptor antagonist, and amrinone - cAMP phosphodiesterase inhibitor). The stimulatory effects of baicalin on epinephrine-induced lipolysis were markedly diminished by insulin (activator of cAMP phosphodiesterases) and H-89 (PKA inhibitor). It was also demonstrated that baicalin evoked a similar rise in epinephrine-induced lipolysis in the presence of glucose and alanine. Our results provided evidence that baicalin may reduce glucose oxidation and is capable of enhancing lipolysis in primary rat adipocytes. The action on lipolysis is glucose-independent and covers both the adrenergic and adenosine A1 receptor pathways. The rise in cAMP content is proposed to be responsible for the observed potentiation of the lipolytic process.
Assuntos
Adipócitos , Flavonoides , Ratos , Animais , Ratos Wistar , Adipócitos/metabolismo , Flavonoides/farmacologia , Lipólise , Epinefrina/farmacologia , Epinefrina/metabolismo , Adenosina/metabolismo , Adenosina/farmacologia , Glucose/metabolismo , Insulina/metabolismoRESUMO
Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Betaína/farmacologia , Betaína/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Resistência à Insulina/fisiologia , RatosRESUMO
Resveratrol (3, 5, 3'-trihydroxystilbene) is a naturally-occurring, biologically active compound having numerous beneficial effects in the organism, including anti-diabetic properties. Its anti-diabetic action have been relatively well established using various animal models, however, in Goto-Kakizaki (GK) rats is poorly explored. These animals are non-obese and have a congenital type 2 diabetes. In the present study, effects of resveratrol on cholesterol content, blood levels of some hormones (thyroxine, triiodothyronine, ghrelin and spexin), glucose and parameters indirectly related with renal function (creatinine, urea nitrogen, total protein and albumin) were explored in GK rats. GK and control rats were treated with resveratrol for 10 weeks at the dose of 20 mg/kg body weight. It was shown that cholesterol content was significantly increased in the blood, liver and the skeletal muscle of diabetic rats, compared with the control animals. However, the resveratrol therapy was associated with a markedly reduced tissue cholesterol content. Our study also demonstrated that blood levels of thyroxine (T4) were decreased, and triiodothyronine (T3) increased in GK rats. These alterations were, however, not significantly affected by resveratrol. GK rats had elevated blood glucose levels, but hyperglycemia was not ameliorated by resveratrol. It was also shown that blood creatinine levels were increased in diabetic rats. However, in animals subjected to the resveratrol therapy, the blood creatinine level was unchanged. Concentrations of ghrelin, spexin and other blood parameters indirectly related with the renal function were shown to be similar in GK and control rats. These results indicate that resveratrol beneficially influences cholesterol concentrations in tissues of diabetic rats; however, it is ineffective in the case of thyroid hormones and glucose. Moreover, it was shown that resveratrol did not induce any significant effects in non-diabetic animals.
Assuntos
Colesterol/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resveratrol/farmacologia , Animais , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/congênito , Modelos Animais de Doenças , Hormônios/sangue , Masculino , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
BACKGROUND: Resveratrol was found to alleviate consequences of some metabolic disturbances which may be due to inappropriate dietary habits. It decreases mortality, increases insulin sensitivity and improves motor functions; these effects are accompanied by reduced plasma leptin and insulin. Leptin plays a significant role in the regulation of food intake and energy expenditure - elevated level in blood is one of the reasons of leptin-resistance and obesity. In this study, the direct effect of resveratrol on leptin secretion from isolated adipocytes was investigated. MATERIAL AND METHODS: Isolated rat adipocytes were incubated with resveratrol (62.5, 125 or 250 microM) and its effects on leptin secretion were studied. Cells were incubated with resveratrol in the presence of glucose (5 and 20 mM) and insulin (10 nM); glucose and nicotinic acid (1 mM); glucose and insulin in the presence of an inhibitor of protein kinase A (H-89, 50 microM) or alanine (10 mM) and insulin. The glucose uptake, glycerol release to the incubation medium, lactate and ATP produced by the cells were also measured. RESULTS: Resveratrol inhibited leptin secretion in all experimental designs in a dose-dependent manner. The effect was not accompanied by changes in glycerol release and glucose uptake. Adipocyte exposure to resveratrol enhanced the lactate formation. It was found that resveratrol dramatically reduced ATP in adipocytes. CONCLUSION: The obtained results revealed the direct ability of resveratrol to reduce leptin secretion from isolated rat adipocytes. Resveratrol is therefore a compound affecting the endocrine function of adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Glucose/metabolismo , Ácido Láctico/metabolismo , Leptina/metabolismo , Estilbenos/farmacologia , Adipócitos/metabolismo , Animais , Células Cultivadas , Masculino , Ratos , Ratos Wistar , ResveratrolRESUMO
Adenosine is secreted from adipocytes, binds to adenosine A(1) receptor and modulates various functions of these cells. In the present study, the effects of an adenosine A(1) receptor antagonist (DPCPX; 0.01, 0.1 and 1 microM) on lipogenesis, glucose transport, lipolysis and the antilipolytic action of insulin were tested in rat adipocytes. DPCPX had a very weak effect on lipogenesis and did not significantly affect glucose uptake. In adipocytes incubated with 1 microM DPCPX, lipolysis increased. This effect was blunted by insulin and by a direct inhibitor of protein kinase A. Moreover, 0.1 microM DPCPX substantially enhanced the lipolytic response to epinephrine and increased cAMP in adipocytes. However, DPCPX was ineffective when lipolysis was stimulated by direct activation of protein kinase A. Adipocyte exposure to epinephrine and insulin with or without 0.1 microM DPCPX demonstrated that this antagonist increased the release of glycerol. However, despite the presence of DPCPX, insulin was able to reduce lipolysis. It is concluded that DPCPX had a weak effect on lipogenesis, whereas lipolysis was significantly affected. The partial antagonism of adenosine A(1) receptor increased lipolysis in cells incubated with epinephrine alone and epinephrine with insulin due to the synergistic action of 0.1 microM DPCPX and epinephrine.
Assuntos
Antagonistas do Receptor A1 de Adenosina , Adenosina/metabolismo , Adipócitos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Xantinas/farmacologia , Adipócitos/metabolismo , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Epinefrina/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Técnicas In Vitro , Insulina/metabolismo , Masculino , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Wistar , Receptor A1 de Adenosina/metabolismoRESUMO
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mammalian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca(2+) concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca(2+) in the regulation of leptin secretion from adipocytes is discussed.
Assuntos
Adipócitos/metabolismo , Leptina/metabolismo , Transdução de Sinais , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , AMP Cíclico/metabolismo , Ácidos Graxos/metabolismo , Retroalimentação Fisiológica , Humanos , Malonil Coenzima A/metabolismo , Proteínas Quinases/metabolismo , Serina-Treonina Quinases TORRESUMO
Resveratrol is a polyphenol found in different plant species and having numerous health-promoting properties in animals and humans. However, its protective action against deleterious effects of ethanol is poorly elucidated. In the present study, the influence of resveratrol (10 mg/kg/day) on some hormones and metabolic parameters was determined in rats ingesting 10 % ethanol solution for two weeks. Blood levels of insulin, glucagon and adiponectin were affected by ethanol, however, resveratrol partially ameliorated these changes. Moreover, in ethanol drinking rats, liver lipid accumulation was increased, whereas resveratrol was capable of reducing liver lipid content, probably due to decrease in fatty acid synthesis. Resveratrol decreased also blood levels of triglycerides and free fatty acids and reduced gamma-glutamyl transferase activity in animals ingesting ethanol. These results show that resveratrol, already at low dose, alleviates hormonal and metabolic changes induced by ethanol in the rat and may be useful in preventing and treating some consequences of alcohol consumption.
Assuntos
Adiponectina/sangue , Etanol/administração & dosagem , Glucagon/sangue , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Etanol/toxicidade , Ácidos Graxos não Esterificados/sangue , Metabolismo dos Lipídeos/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Resveratrol , Triglicerídeos/sangueRESUMO
Mycotoxins-aflatoxin B1 (AFB1) and ochratoxin A (OTA)-compounds which are strong carcinogenic, mutagenic and cytotoxic factors-are also known to evoke a decrease of food intake and body weight gains. The purpose of our study was to determine the direct influence of AFB1 and OTA incubated with isolated rat fat cells on the lipogenesis, lipolysis and leptin secretion. Adipocytes were isolated from the epididymal fat tissue by the collagenase digestion. Toxins used at concentrations 1, 10 and 100 microM were incubated for 90 min with adipocytes. Basal and insulin-stimulated lipogenesis-determined by the measure of [U-14C]glucose conversion to total lipids-was abated by AFB1 only at the highest concentration. At two lower ones, AFB1 did not affect the process. OTA at all used concentrations decreased insulin-stimulated lipogenesis but the effect was not dose-dependent. The lipolysis was determined by the measure of glycerol release from adipocytes. The basal lipolysis was unchanged by both toxins. The epinephrine-stimulated lipolysis was intensified by AFB1 only at the highest concentration, however, the process was not altered by OTA. The antilipolytic action of insulin was unaffected by both compounds (10 microM). To determine the influence of the tested toxins on leptin secretion, adipocytes were incubated for 120 min in the presence of glucose and insulin as stimulators of hormone secretion. AFB1 and OTA added to the incubation medium (1, 10 and 100 microM) had no significant influence on the leptin release. The results obtained in this experiment demonstrate that adipocytes are susceptible to the direct action of AFB1 and OTA. This susceptibility is, however, rather weak and is exhibited by a slight restriction of the lipogenesis (in the case of both toxins) and by a slight increase of the lipolysis (in the case of AFB1).
Assuntos
Adipócitos/efeitos dos fármacos , Aflatoxina B1/toxicidade , Ocratoxinas/toxicidade , Adipócitos/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Epinefrina/farmacologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Leptina/biossíntese , Lipídeos/biossíntese , Lipólise/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
Leptin is an adipocyte-derived hormone participating in the regulation of food intake and energy balance. Its secretion from fat cells is potentiated by insulin and by substrates providing ATP, whereas factors increasing cAMP level attenuate hormone release stimulated by insulin and glucose. The present experiments were aimed to determine the effect of cAMP on leptin secretion stimulated by glucose, alanine or leucine in the presence of insulin. Moreover, the effect of protein kinase A inhibition on leptin secretion was tested. To stimulate leptin secretion, isolated rat adipocytes were incubated for 2 h in the buffer containing 5 mmol/l glucose, 10 mmol/l alanine or 10 mmol/l leucine, all in the presence of 10 nmol/l insulin. Inhibition of protein kinase A (PKA) by H-89 (50 micromol/l) slightly enhanced leptin release stimulated by glucose and leucine but not by alanine. Activation of this enzyme by dibutyryl-cAMP (1 mmol/l) substantially restricted leptin secretion stimulated by glucose, alanine and leucine. The inhibitory influence of dibutyryl-cAMP on leptin secretion was totally (in the case of stimulation induced by glucose) or partially (in the case of stimulation by alanine and leucine) suppressed by H-89. These results demonstrate that leptin secretion induced by glucose, alanine and leucine is profoundly attenuated by cAMP in PKA-dependent manner. Therefore, the action of different stimulators of leptin secretion may be restricted by agents increasing the cAMP content in adipocytes. Moreover, it has also been shown that inhibition of PKA evokes the opposite effect and enhances leptin release.
Assuntos
Adipócitos/enzimologia , Adipócitos/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Leptina/metabolismo , Adipócitos/efeitos dos fármacos , Alanina/farmacologia , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Glucose/farmacologia , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Insulina/farmacologia , Isoquinolinas/farmacologia , Leucina/farmacologia , Masculino , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Wistar , Estimulação Química , Sulfonamidas/farmacologiaRESUMO
Genistein is a phytoestrogen found in several plants eaten by humans and food-producing animals and exerting a wide spectrum of biological activity. In this experiment, the impact of genistein on lipogenesis and lipolysis was studied in isolated rat adipocytes. Incubation of the cells (10(6) cells/ml in plastic tubes at 37 degrees C with Krebs-Ringer buffer, 90 min) with genistein (0.01, 0.3, 0.6 and 1 mM) clearly restricted (1 nM) [U-14C]glucose conversion to total lipids in the absence and presence of insulin. When [14C]acetate was used as the substrate for lipogenesis, genistein (0.01, 0.1 and 1 mM) exerted a similar effect. Thus, the anti-lipogenetic action of genistein may be an effect not only of alteration in glucose transport and metabolism, but this phytoestrogen can also restrict the fatty acids synthesis and/or their esterification. Incubation of adipocytes with estradiol at the same concentrations also resulted in restriction of lipogenesis, but the effect was less marked. Genistein (0.1 and 1 mM) augmented basal lipolysis in adipocytes. This process was strongly restricted by insulin (1 microM) and H-89 (an inhibitor of protein kinase A; 50 microM) and seems to be primarily due to the inhibitory action of the phytoestrogen on cAMP phosphodiesterase in adipocytes. Genistein at the smallest concentration (0.01 mM) augmented epinephrine-stimulated (1 microM) lipolysis but failed to potentiate lipolysis induced by forskolin (1 microM) or dibutyryl-cAMP (1 mM). These results suggest genistein action on the lipolytic pathways before activation of adenylate cyclase. The restriction of lipolysis stimulated by several lipolytic agents--epinephrine, forskolin and dibutyryl-cAMP were observed when adipocytes were incubated with genistein at highest concentrations (0.1 and 1 mM). These results prove the inhibitory action of this phytoestrogen on the final steps of the lipolytic cascade, i.e. on protein kinase A or hormone sensitive lipase. Estradiol, added to the incubation medium, did not affect lipolysis. It can be concluded that genistein significantly affects lipogenesis and lipolysis in isolated rat adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Genisteína/farmacologia , Isoflavonas , Lipídeos/biossíntese , Lipólise/efeitos dos fármacos , Animais , Bucladesina/farmacologia , Colforsina/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Epinefrina/farmacologia , Estradiol/farmacologia , Estrogênios não Esteroides/farmacologia , Humanos , Técnicas In Vitro , Masculino , Fitoestrógenos , Preparações de Plantas , Ratos , Ratos Wistar , Esterol Esterase/antagonistas & inibidoresRESUMO
Aim of the study was to investigate acute leptin effect on insulin blood level and liver insulin binding in the rat. The administration of leptin induced time and dose dependent decrease in the insulin level, which was statistically significant in comparison to the control animals 120 min after administration of higher dose of peptide (0.30 +/- 0.05 vs 0.14 +/- 0.01 nmol/l, respectively). Simultaneously, we have shown the attenuation of liver sensitivity to insulin 2 hours after higher leptin dose injection. This phenomenon was caused by the decrease of binding capacity of high affinity insulin receptor sites (HAIR), which was statistically significant after higher leptin dose administration at both time points (0.54 +/- 0.13 vs 0.26 +/- 0.03 and 0.71 +/- 0.12 vs 0.40 +/- 0.05 pmol/mg protein for 1 and 2 h, respectively). The present study provides evidence that leptin, in addition to its inhibitory effect on insulin secretion, acts as a modulator of insulin receptor, through the decrease of binding capacity. It seems legitimate to suggest that leptin-induced decrease of insulin receptor binding capacity may be one of several causes of insulin resistance.
Assuntos
Insulina/sangue , Fígado/efeitos dos fármacos , Proteínas/farmacologia , Receptor de Insulina/metabolismo , Tecido Adiposo/metabolismo , Animais , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Feminino , Leptina , Fígado/metabolismo , Camundongos , Radioimunoensaio , Ratos , Ratos Wistar , Receptores para Leptina , Proteínas Recombinantes/farmacologia , Fatores de TempoRESUMO
In the performed experiment the effect of alloxan on insulin secretion by in situ perfused rat pancreas was determined. It was found that alloxan added to the perfusion medium results in a sudden, short-term release of insulin. This effect is independent on the presence of glucose (6.66 mmol/l) in the perfusion medium. Furthermore, it was observed that glucose at 16.66 mmol/l concentration after alloxan perfusion does not stimulate insulin secretion.
Assuntos
Aloxano/farmacologia , Insulina/metabolismo , Pâncreas/efeitos dos fármacos , Animais , Glucose/farmacologia , Secreção de Insulina , Masculino , Pâncreas/metabolismo , Ratos , Ratos WistarRESUMO
Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis.
Assuntos
Aloxano/farmacologia , Antibióticos Antineoplásicos/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Ilhotas Pancreáticas/efeitos dos fármacos , Estreptozocina/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Ilhotas Pancreáticas/metabolismo , RatosRESUMO
In order to elucidate the direct effect of glucose on lipolysis in isolated rat adipocytes, cells were incubated in a buffer with different concentrations of this sugar: 2, 8 or 16 mmol/l. The increase in glucose concentration from 2 mmol/l to 8 or 16 mmol/l enhanced basal lipolysis by 30% and 47%, respectively. Epinephrine-induced lipolysis (1 micromol/l) was also increased by 31% and 32%, when glucose concentration was increased from 2 mmol/l to 8 or 16 mmol/l, respectively. The rise in lipolysis caused by glucose was restricted by H-89 (an inhibitor of protein kinase A, 30 micromol/l), but insulin (1 nmol/l) had no inhibitory action. The augmentation of lipolysis by glucose did not require its metabolism (as demonstrated using 2-deoxyglucose) and was due to the action of this sugar on the final steps of the lipolytic cascade, particularly on protein kinase A. However, short-term exposure of adipocytes to higher glucose concentrations did not restrict the inhibitory action of insulin on lipolysis induced by epinephrine.
Assuntos
Adipócitos/efeitos dos fármacos , Glucose/farmacologia , Lipólise , Sulfonamidas , Animais , Separação Celular , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Epinefrina/farmacologia , Insulina/farmacologia , Isoquinolinas/farmacologia , Lipólise/efeitos dos fármacos , Masculino , Concentração Osmolar , Ratos , Ratos WistarRESUMO
Streptozotocin (STZ) is used to induce experimental diabetes in animals and is also applied for the treatment of patients with insulinoma. The aim of the present work was to investigate the direct effect of STZ on lipolysis in isolated rat adipocytes. After the isolation, the cells were incubated in a Krebs-Ringer buffer of pH 7.4, at the temperature 37 degrees C for 90 min with different concentrations of STZ: 0.5, 1 or 2 mmol/l. STZ caused a significant rise in basal values (99%, 199%, and 377%, respectively) and epinephrine-stimulated (1 micromol/l) lipolysis (15%, 24% and 46%, respectively). Augmentation of basal lipolysis by STZ was neither restricted by insulin (1 nmol/l) nor by H-89 (an inhibitor of protein kinase A, 50 micromol/l). These results indicate the stimulatory influence of STZ on the action of hormone-sensitive lipase in isolated cells of white adipose tissue. The obtained outcomes suggest that in studies employing STZ, it is necessary to consider its direct effect upon lipolysis in adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Lipólise/efeitos dos fármacos , Estreptozocina/farmacologia , Sulfonamidas , Adipócitos/citologia , Animais , Inibidores Enzimáticos/farmacologia , Epinefrina/farmacologia , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Insulina/farmacologia , Isoquinolinas/farmacologia , Masculino , Ratos , Ratos Wistar , Simpatomiméticos/farmacologiaRESUMO
Isolated rat adipocytes were incubated with adrenaline, adrenaline plus insulin, alloxan or alloxan plus insulin. Glycerol release was taken as a measure of lipolysis. It was observed that alloxan in the concentration of 3, 10 and 20 mmol/l intensifies lipolysis in adipocytes in the absence of adrenaline. Insulin (10(-6) mol/l) treatment of cells did not inhibit lipolysis caused by this compound, but significantly restricted lipolysis induced by adrenaline (10(-6) mol/l). It was also shown that alloxan in the concentration of 3 and 10 mmol/l intensified lipolysis stimulated by adrenaline (10(-6) mol/l). Addition of 20 mmol/l of alloxan strongly inhibited glycerol release in the presence of adrenaline. The results presented here clearly indicate that the action of alloxan concerns cells of the white adipose tissue.
Assuntos
Adipócitos/metabolismo , Aloxano/farmacologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Lipólise/efeitos dos fármacos , Animais , Células Cultivadas , Interações Medicamentosas , Masculino , Ratos , Ratos WistarRESUMO
The aim of the experiment was to investigate the mechanism of harmful alloxan action in vivo. 75 mg/kg b.w. of this diabetogenic agent were administered to fasting rats. Two minutes later the animals were decapitated. It was observed that alloxan caused a distinct rise in blood insulin and glucose levels with a concomitant drop of free fatty acids. The amount of sulfhydryl groups in the liver of alloxan-treated rats was decreased and glutathione peroxidase activity was substantially higher. These results indicate that some changes observed in alloxan-induced diabetes can not only be the consequence of B cells damage by alloxan but may also be the result of its direct influence on other tissues. It was also observed that glucose given 20 min before alloxan injection only partially protected against the deleterious effects of alloxan.
Assuntos
Aloxano/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Glicemia/metabolismo , Jejum , Ácidos Graxos não Esterificados/sangue , Glutationa Peroxidase/metabolismo , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismoRESUMO
The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic rats was investigated. Three groups of rats were treated with streptozotocin (STZ; 50 mg/kg b.w., intravenously) and one group receiving only saline served as control. Beginning with the third day after STZ treatment, until the last day before decapitation, i.e. for 11 days, two groups of diabetic rats were treated with T3 (50 microg/kg b.w., i.p.) or T4 (250 microg/kg b.w., i.p.). After two weeks, STZ injected rats had lower body weight, hyperglycemia with a simultaneous drop in blood insulin and decrease of T3 and T4 concentrations in comparison to control animals. Liver glycogen content was also reduced, whereas serum lactate, free fatty acids, triglycerides and cholesterol were elevated. Exogenous thyroid hormones given to diabetic rats substantially attenuated hyperglycemia without any significant changes in blood insulin concentration. An additional reduction of body weight gain and depletion in liver glycogen stores were also observed. Thyroid hormones augmented serum lactate and cholesterol and had no beneficial effect on elevated free fatty acids and triglycerides. It can be concluded that in spite of partial restriction of hyperglycemia, thyroid hormones evoked several unfavourable changes strongly limiting their potential use in diabetes.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/sangue , Tiroxina/farmacologia , Tri-Iodotironina/farmacologia , Animais , Metabolismo dos Carboidratos , Diabetes Mellitus Experimental/metabolismo , Metabolismo Energético/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos WistarRESUMO
Sulfhydryl groups, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) are important elements of the antioxidant defence in the organism. The efficacy of their antioxidant action is influenced by many factors. In this work, the effect of fasting on total, protein-bound and nonprotein sulfhydryl groups and on the activity of liver and serum GPx and GST in rats were determined. Male Wistar rats were divided into two groups: non-fasted and 18-hour fasted. In fasted animals liver content of nonprotein sulfhydryl groups (represented predominantly by reduced glutathione; GSH) was diminished by 22% in comparison to non-fasted group, whereas total and protein-bound -SH groups were unaffected. The activity of liver and serum GPx was unchanged in food deprived rats. In these animals the activity of GST in serum was reduced by 26%. Fasting had no significant effect on the activity of GST in the liver. Our results demonstrate that in rats deprived of food for 18 hours liver and serum GPx and GST are not involved in protection against action of reactive oxygen species formed during fasting. The observed drop in the content of liver nonprotein sulfhydryl groups without concomitant rise in the activity of GPx and GST indicates that this effect may be due to augmented degradation of GSH, its potentiated efflux from hepatocytes and formation of conjugates with intermediates arising as a result of reactive oxygen species action.
Assuntos
Jejum , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Fígado/metabolismo , Compostos de Sulfidrila/metabolismo , Animais , Glutationa Transferase/sangue , Fígado/enzimologia , Masculino , Ratos , Ratos WistarRESUMO
Myo-inositol was found to possess several beneficial effects on the organism. The effect of myo-inositol on ethanol-induced metabolic changes and insulin concentration was investigated in growing rats. The increase in liver triglycerides induced by ethanol drinking (10% ethanol solution as the only drinking fluid for 10 days) was completely abolished by simultaneous treatment with myo-inositol (0. 1 g/100 g b.w., every day given intragastrically). The ethanol-evoked decrease in blood insulin and the increase in liver glycogen were also partially prevented by myo-inositol. Myo-inositol did not cause any undesirable metabolic changes in the rats. The results indicate that myo-inositol may be useful in the treatment of some metabolic consequences of alcohol drinking.