Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats

• Published in: Life sciences (1973) 2018-04, Vol.199, p.158-166
• Main Authors: Oliveira, Ariclecio Cunha de, Andreotti, Sandra, Sertie, Rogério António Laurato, Campana, Amanda Baron, de Proença, André Ricardo Gomes, Vasconcelos, Renata Prado, Oliveira, Keciany Alves de, Coelho-de-Souza, Andrelina Noronha, Donato-Junior, José, Lima, Fábio Bessa
• Format: Article
• Language: English
• Subjects: Abnormalities; Adipocytes; Adipose tissue; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Androgen receptors; Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; Body weight; Combined treatment; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Drinking water; Drug Therapy, Combination; Gene expression; Glucose; Glycemic Index - drug effects; Glycemic Index - physiology; Hypogonadism; Hypothalamic-pituitary-gonadal axis; Hypothalamus; Insulin; Insulin - administration & dosage; Kiss1 protein; Lipids; Male; Melatonin; Melatonin - administration & dosage; Metabolic disorders; Metabolism; Morphometry; Neonates; Neuroblastoma; Neurokinin; Neurokinin B; Oxidation; Pituitary; Pituitary-gonadal axis; Rats; Rats, Wistar; Reproduction - drug effects; Reproduction - physiology; Sleep apnea; Sleep disorders; Streptozocin; Treatment Outcome; Tumors
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2018.02.040

Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function.