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Calorie restriction reduces pinealectomy‐induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane
Author(s) -
Zanquetta Melissa M.,
Seraphim Patricia M.,
Sumida Doris H.,
CipollaNeto Jose,
Machado Ubiratan F.
Publication year - 2003
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2003.00067.x
Subject(s) - glut4 , medicine , endocrinology , insulin resistance , pinealectomy , calorie restriction , glucose transporter , melatonin , biology , insulin , insulin tolerance test , pineal gland , insulin sensitivity
The present study aimed to investigate insulin sensitivity and GLUT4 expression protein in pinealectomized rats, as well as to determining the effects of melatonin and calorie restriction on the changes induced by pinealectomy. Wistar rats were pinealectomized (Pinx) or sham operated (Sham), and studied 30 days later. Melatonin replacement treatment (50 g/100 g body weight) was continued for 30 days after pinealectomy. Calorie restriction was performed by offering 60% of the standard food intake. In vivo insulin sensitivity was evaluated using the glucose disappearance constant (kITT) during an insulin tolerance test, and GLUT4 mRNA and protein were assessed by Northern and Western blotting, respectively. The in vitro effect of melatonin on GLUT4 protein content in plasma membrane was investigated in adipocytes isolated from intact rats. Compared with Sham rats, Pinx rats showed decreased kITT (40%), GLUT4 expression in white adipose tissue (WAT, ∼70%), and unchanged GLUT4 expression in skeletal muscle. Melatonin treatment in Pinx rats restored the kITT and GLUT4 protein to control values. No in vitro effects of melatonin (10 −9 m ) upon GLUT4 protein were observed. Calorie restriction of Pinx rats increased their kITT value (∼40%), total GLUT4 protein content (∼240%) and its translocation to the plasma membrane (∼80%) in WAT. The results show that pinealectomy, for lack of melatonin, decreased insulin sensitivity as well as GLUT4 gene expression. Calorie restriction improved insulin sensitivity in Pinx rats, and this was related to increased GLUT4 gene expression and insulin‐induced GLUT4 translocation to the plasma membrane in WAT.