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Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the <jats:styled-content style=\"fixed-case\">ISP<\/jats:styled-content>, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8\u2010 and 12\u00a0wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1\u2010fold increase both after 8\u2010 and 12\u00a0wk of melatonin supplementation. Animals supplemented with melatonin for 12\u00a0wk also presented a reduction in body mass. The acute insulin\u2010induced phosphorylation of the analyzed <jats:styled-content style=\"fixed-case\">ISP<\/jats:styled-content> proteins increased 1.3\u2010 and 2.3\u2010fold after 8\u2010 and 12\u00a0wk of melatonin supplementation. The total protein content of the insulin receptor (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>) and the <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> substrates (<jats:styled-content style=\"fixed-case\">IRS<\/jats:styled-content>\u20101, 2) remained unchanged in all investigated tissues, except for the 2\u2010fold increase in the total amount of <jats:styled-content style=\"fixed-case\">IRS<\/jats:styled-content>\u20101 in the periepididymal adipose tissue. Therefore, the known age\u2010related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.<\/jats:p>","DOI":"10.1111\/jpi.12056","type":"journal-article","created":{"date-parts":[[2013,3,30]],"date-time":"2013-03-30T12:18:43Z","timestamp":1364645923000},"page":"156-165","source":"Crossref","is-referenced-by-count":75,"title":["Melatonin improves insulin sensitivity independently of weight loss in old obese rats"],"prefix":"10.1111","volume":"55","author":[{"given":"Ricardo","family":"Zanuto","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences\u2010I University of S\u00e3o Paulo (USP) S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rio A.","family":"Siqueira\u2010Filho","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences\u2010I University of S\u00e3o Paulo (USP) S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana C.","family":"Caperuto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Federal University of S\u00e3o Paulo (UNIFESP) Diadema SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reury F. 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