Ranolazine: a Potential Anti-diabetic Drug

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Virginia Tech

Diabetes is a life-long chronic disease that affects more than 24 million Americans. Loss of pancreatic beta-cell mass and function is central to the development of both type 1 (T1D) and type 2 diabetes (T2D). Therefore, preservation or regeneration of functional beta-cell mass is one of the essential strategies to treat diabetes [1]. In my study, I tested if ranolazine, a synthetic compound, has potential to prevent or treat diabetes. Diabetes were induced in mice by giving multiple low-doses of streptozotocin (STZ). Ranolazine was given twice daily via an oral gavage (20 mg/kg) for 5 weeks. blood levels of glucose, insulin, and glycosylated hemoglobin (HbA1c) were measured. Glucose tolerance test was performed in control and treated mice. pancreatic tissues were stained with hematoxylin and eosin or stained with insulin antibody for islet mass evaluation. INS1-832/13 cells and human islets were further used to evaluate the effect of ranalozine on beta-cell survival and related signaling pathway. Fasting blood glucose levels after the fourth week of STZ injections were lower in ranolazine treated group (199.1 mg/dl) compared to the vehicle group (252.1 mg/dl) (p<0.01). HbA1c levels were reduced by ranolozine treatment (5.33%) as compared to the control group (7.23%) (p<0.05%). Glucose tolerance was improved in ranolazine treated mice (p<0.05). Mice treated with ranolazine had higher beta-cell mass (0.25%) than the vehicle group (0.07%)(p<0.01). In addition, ranolazine improved survival of human islets exposed to high levels of glucose and palmitate, whereas cell proliferation was not altered. In addition, ranolazine slightly increased the cAMP in MIN-6 cell and human islets. In conclusion, ranolazine may have therapeutic potential for diabetes by preserving beta-cell mass.

Ranolazine, Beta-cell, Apoptosis, Proliferation, Diabetes