المصدر: PLoS ONE

مصطلحات موضوعية: eprotirome, hormone receptor stimulating agent, liothyronine, sobetirome, thyroid hormone receptor, thyroid hormone receptor agonist, triacylglycerol, unclassified drug, 3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid, acetic acid derivative, anilide, glucose 6 phosphatase, glucose blood level, phenol derivative, animal experiment, animal model, animal tissue, Article, body temperature, controlled study, glucose tolerance, glycemic control, insulin resistance, insulin sensitivity, liver level, male, mouse, nonalcoholic fatty liver, nonhuman, ob/ob mouse

الوصف: Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered. © 2015 Martagón et al.

وصف الملف: application/pdf

العلاقة: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84927551485&doi=10.1371%2fjournal.pone.0122987&partnerID=40&md5=14f9f5ca9792af91731933c252de5f59Test; Investigadores; Estudiantes; http://hdl.handle.net/11285/630522Test; 10

الإتاحة: https://doi.org/10.1371/journal.pone.0122987Test
http://hdl.handle.net/11285/630522Test

المؤلفون: de Moura, Leandro Pereira, Souza Pauli, Luciana Santos, Cintra, Dennys Esper, de Souza, Claudio Teodoro, da Silva, Adelino Sanchez Ramos, Marinho, Rodolfo, de Melo, Maria Alice Rostom, Ropelle, Eduardo Rochete, Pauli, José Rodrigo

المساهمون: Universidade Estadual Paulista (UNESP)

مصطلحات موضوعية: glucose, glucose 6 phosphatase, insulin, insulin receptor, insulin receptor beta, insulin receptor substrate 1, protein tyrosine phosphatase 1B, unclassified drug, aging, animal experiment, controlled study, diet restriction, enzyme blood level, enzyme regulation, epididymis fat, exercise, glucose blood level, groups by age, insulin blood level, insulin sensitivity, insulin tolerance test, liver, molecular mechanics, nonhuman, priority journal, rat, signal transduction, swimming

الوصف: It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

العلاقة: Immunity and Ageing; 4.019; 1,218; http://dx.doi.org/10.1186/1742-4933-10-8Test; Immunity and Ageing, v. 10, n. 1, 2013.; http://hdl.handle.net/11449/74628Test; WOS:000327218400001; 2-s2.0-84874150350; 2-s2.0-84874150350.pdf

الإتاحة: https://doi.org/10.1186/1742-4933-10-8Test
http://hdl.handle.net/11449/74628Test

المؤلفون: Paul Webb, Jean Z. Lin, Kevin J. Phillips, Alexandro J. Martagón, Stephanie L. Cimini

المصدر: PLoS ONE
PLoS ONE, Vol 10, Iss 4, p e0122987 (2015)

مصطلحات موضوعية: Blood Glucose, Male, Time Factors, glucose tolerance, medicine.medical_treatment, lcsh:Medicine, Mice, Obese, ob/ob mouse, Acetates, mouse mutant, Body Temperature, chemistry.chemical_compound, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, dose response, time factor, animal, Anilides, lcsh:Science, 0303 health sciences, Multidisciplinary, Receptors, Thyroid Hormone, Fatty liver, Mus, 3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid, thyroid hormone receptor agonist, 3. Good health, sobetirome, unclassified drug, 030220 oncology & carcinogenesis, Enzyme Induction, Glucose-6-Phosphatase, acetic acid derivative, triacylglycerol, Research Article, medicine.medical_specialty, glucose 6 phosphatase, phenol derivative, animal experiment, Biology, hormone receptor stimulating agent, anilide, Article, animal tissue, 03 medical and health sciences, Insulin resistance, Phenols, Internal medicine, eprotirome, medicine, nonalcoholic fatty liver, insulin sensitivity, Animals, controlled study, mouse, 030304 developmental biology, Thyroid hormone receptor, nonhuman, Triglyceride, Dose-Response Relationship, Drug, Insulin, animal model, lcsh:R, thyroid hormone receptor, medicine.disease, Endocrinology, glucose blood level, Eprotirome, chemistry, 7 INGENIERÍA Y TECNOLOGÍA, drug effects, glycemic control, liver level, agonists, lcsh:Q, Steatosis, liothyronine, biosynthesis, Insulin Resistance, metabolism

الوصف: Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered. © 2015 Martagón et al.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1fa2be68e31853969fca73179e37f167Test
https://pubmed.ncbi.nlm.nih.gov/25849936Test

المؤلفون: de Moura, Leandro Pereira, Souza Pauli, Luciana Santos, Cintra, Dennys Esper, de Souza, Claudio Teodoro, da Silva, Adelino Sanchez Ramos, Marinho, Rodolfo, de Melo, Maria Alice Rostom, Ropelle, Eduardo Rochete, Pauli, José Rodrigo

المساهمون: Universidade Estadual Paulista (UNESP)

مصطلحات موضوعية: glucose, glucose 6 phosphatase, insulin, insulin receptor, insulin receptor beta, insulin receptor substrate 1, protein tyrosine phosphatase 1B, unclassified drug, aging, animal experiment, controlled study, diet restriction, enzyme blood level, enzyme regulation, epididymis fat, exercise, glucose blood level, groups by age, insulin blood level, insulin sensitivity, insulin tolerance test, liver, molecular mechanics, nonhuman, priority journal, rat, signal transduction, swimming

الوصف: It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

العلاقة: Immunity and Ageing; Immunity and Ageing, v. 10, n. 1, 2013.; http://hdl.handle.net/11449/74628Test; http://acervodigital.unesp.br/handle/11449/74628Test; WOS:000327218400001; 2-s2.0-84874150350.pdf; 2-s2.0-84874150350; http://dx.doi.org/10.1186/1742-4933-10-8Test

الإتاحة: https://doi.org/10.1186/1742-4933-10-8Test
http://acervodigital.unesp.br/handle/11449/74628Test
http://hdl.handle.net/11449/74628Test

المؤلفون: Claudio Teodoro de Souza, Adelino Sanchez Ramos da Silva, Eduardo R. Ropelle, Maria Alice Rostom de Melo, Rodolfo Marinho, José Rodrigo Pauli, Luciana Santos Souza Pauli, Leandro Pereira de Moura, Dennys E. Cintra

المساهمون: Universidade Estadual Paulista (Unesp), Universidade Estadual de Campinas (UNICAMP), Laboratório de Bioquímica e Fisiologia, Universidade de São Paulo (USP)

المصدر: Immunity & Ageing : I & A
Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP

مصطلحات موضوعية: Aging, insulin tolerance test, medicine.medical_treatment, ENVELHECIMENTO, groups by age, insulin blood level, rat, glucose, insulin receptor, swimming, exercise, biology, molecular mechanics, unclassified drug, priority journal, enzyme regulation, medicine.symptom, diet restriction, signal transduction, Glucose 6-phosphatase, glucose 6 phosphatase, insulin, medicine.medical_specialty, animal experiment, Phosphatase, Immunology, Inflammation, liver, enzyme blood level, Insulin resistance, Internal medicine, medicine, epididymis fat, insulin sensitivity, controlled study, nonhuman, business.industry, Insulin, Research, aging, Insulin tolerance test, insulin receptor substrate 1, medicine.disease, IRS1, Insulin receptor, Ageing, glucose blood level, Endocrinology, insulin receptor beta, biology.protein, protein tyrosine phosphatase 1B, business

الوصف: Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:42:51Z : No. of bitstreams: 1 2-s2.0-84874150350.pdf: 1076653 bytes, checksum: 37e4bf08d3dc8c43747910da4ae5248a (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-25 It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd. Universidade Estadual Paulista UNESP Curso de Pós-Graduação em Ciências da Motricidade Humana, Rio Claro, SP Faculdade de Ciências Aplicadas Universidade Estadual de Campinas Curso de Pós-Graduação em Nutrição, Esporte e Metabolismo. UNICAMP, Limeira, SP Universidade do Extremo Sul Catarinense Laboratório de Bioquímica e Fisiologia, Santa Catarina, Criciúma, SC Universidade de São Paulo Escola de Educação Física e Esporte USP, Ribeirão Preto, SP Curso de Ciências do Esporte FCA-UNICAMP, Rua Pedro Zaccaria, 1300, Jardim Santa Luzia, Limeira, SP Universidade Estadual Paulista UNESP Curso de Pós-Graduação em Ciências da Motricidade Humana, Rio Claro, SP

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3f7ef7557f049f5bcd04a3e6d28a3a5Test
https://pubmed.ncbi.nlm.nih.gov/23442260Test

المؤلفون: Mazzetti, M.B., Taira, M.C., Lelli, S.M., Dascal, E., Basabe, J.C., De Viale, L.C.S.M.

مصطلحات موضوعية: Gluconeogenesis, Glucose, Hexachlorobenzene, Insulin, Porphyria cutanea tarda, glucose 6 phosphatase, glycogen, phosphoenolpyruvate carboxykinase (GTP), pyruvate carboxylase, pyruvate kinase, animal cell, animal experiment, animal model, animal tissue, article, controlled study, evaluation, female, glucose blood level, glucose metabolism, glycogen liver level, insulin blood level, nonhuman, oxidative stress, priority journal, rat, Animals, Disease Models, Animal, Enzyme Inhibitors

الوصف: Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative response of the organism to stimulate ...

العلاقة: http://hdl.handle.net/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest

الإتاحة: https://doi.org/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest
https://hdl.handle.net/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest

المؤلفون: Mazzetti, Marta Blanca, Taira, María Cristina, Lelli de Angeletti, Sandra Marcela

مصطلحات موضوعية: Gluconeogenesis, Glucose, Hexachlorobenzene, Insulin, Porphyria cutanea tarda, glucose 6 phosphatase, glycogen, phosphoenolpyruvate carboxykinase (GTP), pyruvate carboxylase, pyruvate kinase, animal cell, animal experiment, animal model, animal tissue, article, controlled study, evaluation, female, glucose blood level, glucose metabolism, glycogen liver level, insulin blood level, nonhuman, oxidative stress, priority journal, rat, Animals, Disease Models, Animal, Enzyme Inhibitors

الوصف: Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative response of the organism to stimulate ...

العلاقة: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v78_n1_p25_MazzettiTest; http://hdl.handle.net/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest

الإتاحة: https://doi.org/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v78_n1_p25_MazzettiTest
https://hdl.handle.net/20.500.12110/paper_03405761_v78_n1_p25_MazzettiTest