Insulin Replacement Therapy for the Rat Model of Streptozotocin-Induced Diabetes Mellitus

Objective: This study was conducted to compare various strategies for insulin replacement therapy in the streptozotocin-induced diabetic rat model.

Methods: Control and diabetic Sprague Dawley rats were fed ad libitum, blood glucose concentration was measured twice daily, and outcome was assessed over the final 5 days of a 10-day treatment period, with adjustment of insulin dosage toward the goal of normal glucose values.

Results: All insulin regimens induced weight gain at least comparable to that of controls, but glucose regulation differed. It was not possible to normalize glucose values by use of protamine zinc insulin (PZI) or Ultralente insulin given once daily. In contrast, PZI and neutral protamine Hagedorn (NPH) insulin given twice daily provided glucose values comparable to those in controls, whereas glucose values were modestly higher in response to a 70% human insulin isophane suspension and 30% soluble human insulin solution (70/30 insulin) given twice daily. Attempted normalization of glucose values was limited by hypoglycemia, which was most common after administration of PZI once daily, and least common after 70/30 insulin given twice daily. Dosage requirements for Ultralente insulin were four- to fivefold higher than those for all other insulins.

Conclusion: In streptozotocin-diabetic rats, normal weight gain can be achieved by treatment with PZI insulin once daily, but attainment of near-normal glucose values requires administration of PZI, NPH, or 70/30 insulin twice daily. Ultralente insulin may have reduced bioeffectiveness in this animal model.