Intravenous Infusions of Sulfated Insulin Normalize Plasma Glucose Levels in Pancreatectomized Dogs

Sulfated insulin (SI) differs radically from regular crystalline zinc insulin (CZI). To date, SI has been used mainly for the subcutaneous treatment of diabetics with resistance or local allergic reactions to CZI. In this regard, SI exists as a soluble monomer at pH 7.4 and is not inclined to self-association even when agitated and exposed for long periods to materials known to aggregate CZI. To compare its stability and biologic activity when used in conjunction with intravenous infusion pumps, diabetic dogs were infused portally for 140 days with SI and for 140 days with CZI. These studies demonstrated a significant improvement of glycemie control obtainable with SI compared with CZI. Mean ± SD fasting glycemias were normalized for the SI group (99 ± 19 mg/dl) and were significantly (P < 0.001) less than the mean of 148 ± 64 mg/dl for the CZI group. Mean ± SD coefficient of variation of the fasting plasma glucose concentrations was 18 ± 1% for the SI- versus 43 ± 3% for the CZI-infused dogs, both significantly greater than normal values of 4.5 ± 0.5%. Basal insulin requirements under these conditions also differed significantly (P < 0.001). The CZI group received 0.35 ± 0.07 mU/kg/min compared with 0.20 ± 0.05 mU/kg/min for the SI group¹, the former resulted in mean ± SD plasma levels of 14 ± 7 μU/ml and the latter resulted in concentrations of 47 ± 12 μU/ml. Insulin clearance rates were 28 ± 11 ml/kg/min with CZI compared with 5 ± 3 ml/kg/min with SI (P < 0.001). CZI but not SI resulted in progressive obstruction of the delivery systems employed. In conclusion, porcine SI is more stable and remarkably more resistant to aggregation than regular CZI preparations. It maintains its bioactivity and affords improved long-term glycemie control when infused . v. With SI insulin requirements were reduced 1.75-fold while insulin clearance was reduced 5.6-fold compared with CZI. These findings reflect the essentially mono-meric nature of the hormone and emphasize its remarkable stability in the difficult environment presented by a portable pumping system.