Endocrine Abstracts

Mildronate, a γ-butyrobetaine analogue is actually used as an antiischemic drug. It was also shown to have effect on mechanisms of glucose utilization.

Methods: Diabetes mellitus in Wistar rats was induced by injection of streptozotocin (50 mg/kg). Experimental rats were treatment with Mildronate (100 mg/kg daily, per os) for 6 weeks. Weight, blood glucose concentration, blood triglyceride concentration, blood ketone body concentration, glycated hemoglobin percent (HbA1c%), glucose tolerance were monitored throughout the experiment. iNOS gene expression was evaluated by qRT-PCR in heart, muscle, liver and kidney of diabetic animals.

Results: In diabetic rats, Mildronate treatment caused a significant decrease in mean blood glucose concentration after 4 weeks of treatment (streptozotocin group – 40.27±3.34 mmol/l, streptozotocin+Mildronate group – 29.82±2.12 mmol/l). Mildronate produced positive effect on triglyceride level in diabetic rats: after 4, 5 and 6 weeks of treatment streptozotocin+Mildronate group showed lower triglyceride levels, than streptozotocin group (after 4 weeks – 1.29±0.10 vs 1.91±0.26 mmol/l; after 5 weeks – 1.04±0.03 vs 1.23±0.08 mmol/l; after 6 weeks – 1.12±0.09 vs 1.77±0.30 mmol/l). Mildronate was able to slow down significantly the rise of HbA1c% in treated diabetic group (after 6 weeks of treatment HbA1c% in streptozotocin group – 9.66±0.21%, in streptozotocin+Mildronate group – 8.75±0.33%). Oral glucose tolerance test after 4 treatment weeks revealed significantly better glucose tolerance in streptozotocin+Mildronate group at 120 min after glucose ingestion. iNOS gene expression was altered by Mildronate treatment in liver, muscle and heart. This might indicate on stimulatory effect of Mildronate on insulin-independent glucose transport in tissues of diabetic rats.

Conclusion: Mildronate improves carbohydrate metabolism in experimental diabetes mellitus model, possibly via insulin-independent mechanisms.