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

Abstract

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 glycemic 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 less than 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 less than 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 group, the former resulted in mean +/- SD plasma levels of 14 +/- 7 microU/ml and the latter resulted in concentrations of 47 +/- 12 microU/ml. Insulin clearance rates were 28 +/- 11 ml/kg/min with CZI compared with 5 +/- 3 ml/kg/min with SI (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Counterregulatory Hormone Responses Preserved After Long-Term Intravenous Insulin Infusion Compared to Continuous Subcutaneous Insulin Infusion

“…During the period of IV, sulfated pork insulin (28,29) was administered using a microprocessor-based portable intravenous infusion system as previously described (30)(31)(32). The basal and three-pulse waveforms of mealtime insulin infusion were adjusted to achieve similar target glucose levels (33).…”

Controlled Crossover Study of Subcutaneous and Intravenous Insulin Infusion in Type I Diabetes

“…The controller was programmed by a physician using a modified hand-held HewlettPackard 41CV calculator. Sulfated pork insulin (Connaught, Toronto), which has less tendency to self-associate in dilute solution (29,30), was diluted to a final concentration of 2 U/ml in bacteriostatic water (0.9% benzyl alcohol) containing 10 raM Tris-HCl buffer adjusted to pH 7.4-The SC and IV insulin-infusion patterns are contrasted schematically in Fig. 1.…”

Preprogrammed Intravenous Insulin Infusion in Diabetic Humans: Metabolic Consequences of Altering Meal Size

“…Sulfated beef insulin (Connaught Laboratories, Willowdale, Ontario, Canada), which had been shown to be physicochemically stable with less tendency to selfassociate in dilute solution, 14 was diluted to a final concentration of 2 U/ml in bacteriostatic water (0.9% benzyl alcohol) containing 10 mM Tris buffer, and pH was adjusted to 7.4. The reservoir was refilled two to three times a week through two cascaded bacterial filters of 0.22-|xm pore size (Millipore, Bedford, MA).…”