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Published on: December 7, 2017
Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its
Melissa M Zanquetta1, Patricia M Seraphim, Doris H Sumida
1Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Abstract:
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, approximately 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 ( approximately 40%), total GLUT4 protein content ( approximately 240%) and its translocation to the plasma membrane ( approximately 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.
Insights
Pinealectomy reduces insulin sensitivity and glucose transporter type 4 (GLUT4) expression due to melatonin deficiency. Both melatonin replacement and calorie restriction in pinealectomized rats improve insulin sensitivity and GLUT4 regulation.
Area of Science:
- Endocrinology
- Metabolic Research
- Chronobiology
Background:
- Pinealectomy disrupts circadian rhythms and melatonin production.
- Melatonin plays a role in metabolic regulation.
- Insulin sensitivity is crucial for glucose homeostasis.
Purpose of the Study:
- Investigate insulin sensitivity and GLUT4 expression in pinealectomized rats.
- Determine the effects of melatonin and calorie restriction on these parameters.
- Elucidate the role of melatonin in metabolic regulation.
Main Methods:
- Pinealectomy and sham surgery in Wistar rats.
- Melatonin replacement and calorie restriction interventions.
- In vivo insulin tolerance tests (kITT).
- Western blotting and Northern blotting for GLUT4 mRNA and protein analysis.
Main Results:
- Pinealectomized rats exhibited reduced insulin sensitivity and GLUT4 expression in white adipose tissue.
- Melatonin treatment restored insulin sensitivity and GLUT4 levels.
- Calorie restriction significantly improved insulin sensitivity and GLUT4 expression/translocation in white adipose tissue.
Conclusions:
- Melatonin deficiency following pinealectomy impairs insulin sensitivity and GLUT4 expression.
- Melatonin replacement can reverse these metabolic deficits.
- Calorie restriction offers a potential therapeutic strategy for improving metabolic health in conditions of melatonin deficiency.
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