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Objective: The aim of this study was investigating the potential effect of subacute mianserin administration on diabetes-induced chronic hyperglycemia and metabolic alterations.
Methods: Male Wistar rats of the same age (weight: 250-300 g) were used for the experiments. Diabetes was induced by a single 50 mg/ kg dose of intravenous streptozotocine (STZ) administration. Effects of 14 days mianserin (30 and 45 mg/kg) administration on hyperglycemia arising in 6-week-diabetic rats were assessed by conducting oral glucose tolerance tests (OGTT) and by measuring glycated hemoglobin (HbA1c) levels. Changes in metabolic parameters such as food and water consumption and urine and feces excretion were observed using metabolic cages. Body weights of the animals were recorded weekly. Possible effect of mianserin treatment on Ins1 mRNA expression of diabetic rats was evaluated by real-time polymerase chain reaction (PCR) method. The experimental protocol was approved by the Anadolu University Animal Experiments Local Ethics Committee.
Results: Fourteen-daysubacute administration of mianserin did not alter the OGTT results or HbA1c levels of normoglycemic animals. Similarly, mianserin caused significant alterations neither in the measured metabolic parameters nor in the body weights of normoglycemic rats. On the other hand, subacute administration of this drug to the diabetic animals significantly reduced the augmented HbA1c levels with respect to the untreated diabetic groups. Further, mianserin treatment caused significant reduction in the increased urine discharge, fecal output, water, and food consumption characteristic of diabetic animals. Weight loss of diabetic animals was also improved. With regard to the anti-hyperglycemic effect, mianserin administered at a dose of 30 mg/kg was found to be as effective as the reference drug metformin (dose, 1g/kg). Moreover, our real-time PCR results indicated that Ins1 mRNA expression levels of diabetic rats significantly decreased with respect to the normoglycemic rats, as expected. Mianserin administration significantly increased the reduced levels of Ins1 gene expression in diabetic animals. Our data obtained from this study indicated that subacute administration of mianserin has a remarkable anti-hyperglycemic effect on STZ-induced long-term hyperglycemia. Further, this drug has a notable beneficial effect on chronic hyperglycemia-induced polydipsia, polyuria, polyphagia and weight loss. The observed anti-hyperglycemic effect of mianserin in this study seems to be mediated by an increase in insulin synthesis. Nevertheless, additional studies, such as examining the alterations in expressions of other related genes or measuring the levels of synthesized insulin by Western-blot method, are needed to verify this idea.
Conclusion: To the best of our knowledge, this is the first study to show that the anti-hyperglycemic effect of mianserin, an atypical antidepressant, in the experimental diabetes model was comparable to those of the reference drugs metformin. Considering that mianserin simultaneously exhibits antidepressant and anti-hyperglycemic effects, it seems that this drug could have an additional advantage for diabetic patients for treating the mood disorders caused by diabetes.